diff --git a/rlp/decode.go b/rlp/decode.go
index c9b265241..c9b50e8c1 100644
--- a/rlp/decode.go
+++ b/rlp/decode.go
@@ -29,6 +29,7 @@ import (
 	"sync"
 
 	"github.com/ethereum/go-ethereum/rlp/internal/rlpstruct"
+	"github.com/holiman/uint256"
 )
 
 //lint:ignore ST1012 EOL is not an error.
@@ -52,6 +53,7 @@ var (
 	errUintOverflow  = errors.New("rlp: uint overflow")
 	errNoPointer     = errors.New("rlp: interface given to Decode must be a pointer")
 	errDecodeIntoNil = errors.New("rlp: pointer given to Decode must not be nil")
+	errUint256Large  = errors.New("rlp: value too large for uint256")
 
 	streamPool = sync.Pool{
 		New: func() interface{} { return new(Stream) },
@@ -148,6 +150,7 @@ func addErrorContext(err error, ctx string) error {
 var (
 	decoderInterface = reflect.TypeOf(new(Decoder)).Elem()
 	bigInt           = reflect.TypeOf(big.Int{})
+	u256Int          = reflect.TypeOf(uint256.Int{})
 )
 
 func makeDecoder(typ reflect.Type, tags rlpstruct.Tags) (dec decoder, err error) {
@@ -159,6 +162,10 @@ func makeDecoder(typ reflect.Type, tags rlpstruct.Tags) (dec decoder, err error)
 		return decodeBigInt, nil
 	case typ.AssignableTo(bigInt):
 		return decodeBigIntNoPtr, nil
+	case typ == reflect.PtrTo(u256Int):
+		return decodeU256, nil
+	case typ == u256Int:
+		return decodeU256NoPtr, nil
 	case kind == reflect.Ptr:
 		return makePtrDecoder(typ, tags)
 	case reflect.PtrTo(typ).Implements(decoderInterface):
@@ -235,6 +242,24 @@ func decodeBigInt(s *Stream, val reflect.Value) error {
 	return nil
 }
 
+func decodeU256NoPtr(s *Stream, val reflect.Value) error {
+	return decodeU256(s, val.Addr())
+}
+
+func decodeU256(s *Stream, val reflect.Value) error {
+	i := val.Interface().(*uint256.Int)
+	if i == nil {
+		i = new(uint256.Int)
+		val.Set(reflect.ValueOf(i))
+	}
+
+	err := s.ReadUint256(i)
+	if err != nil {
+		return wrapStreamError(err, val.Type())
+	}
+	return nil
+}
+
 func makeListDecoder(typ reflect.Type, tag rlpstruct.Tags) (decoder, error) {
 	etype := typ.Elem()
 	if etype.Kind() == reflect.Uint8 && !reflect.PtrTo(etype).Implements(decoderInterface) {
@@ -863,6 +888,45 @@ func (s *Stream) decodeBigInt(dst *big.Int) error {
 	return nil
 }
 
+// ReadUint256 decodes the next value as a uint256.
+func (s *Stream) ReadUint256(dst *uint256.Int) error {
+	var buffer []byte
+	kind, size, err := s.Kind()
+	switch {
+	case err != nil:
+		return err
+	case kind == List:
+		return ErrExpectedString
+	case kind == Byte:
+		buffer = s.uintbuf[:1]
+		buffer[0] = s.byteval
+		s.kind = -1 // re-arm Kind
+	case size == 0:
+		// Avoid zero-length read.
+		s.kind = -1
+	case size <= uint64(len(s.uintbuf)):
+		// All possible uint256 values fit into s.uintbuf.
+		buffer = s.uintbuf[:size]
+		if err := s.readFull(buffer); err != nil {
+			return err
+		}
+		// Reject inputs where single byte encoding should have been used.
+		if size == 1 && buffer[0] < 128 {
+			return ErrCanonSize
+		}
+	default:
+		return errUint256Large
+	}
+
+	// Reject leading zero bytes.
+	if len(buffer) > 0 && buffer[0] == 0 {
+		return ErrCanonInt
+	}
+	// Set the integer bytes.
+	dst.SetBytes(buffer)
+	return nil
+}
+
 // Decode decodes a value and stores the result in the value pointed
 // to by val. Please see the documentation for the Decode function
 // to learn about the decoding rules.
diff --git a/rlp/decode_test.go b/rlp/decode_test.go
index dbcfcffed..07d9c579a 100644
--- a/rlp/decode_test.go
+++ b/rlp/decode_test.go
@@ -28,6 +28,7 @@ import (
 	"testing"
 
 	"github.com/ethereum/go-ethereum/common/math"
+	"github.com/holiman/uint256"
 )
 
 func TestStreamKind(t *testing.T) {
@@ -468,6 +469,10 @@ var (
 	veryVeryBigInt = new(big.Int).Exp(veryBigInt, big.NewInt(8), nil)
 )
 
+var (
+	veryBigInt256, _ = uint256.FromBig(veryBigInt)
+)
+
 var decodeTests = []decodeTest{
 	// booleans
 	{input: "01", ptr: new(bool), value: true},
@@ -541,11 +546,27 @@ var decodeTests = []decodeTest{
 	{input: "89FFFFFFFFFFFFFFFFFF", ptr: new(*big.Int), value: veryBigInt},
 	{input: "B848FFFFFFFFFFFFFFFFF800000000000000001BFFFFFFFFFFFFFFFFC8000000000000000045FFFFFFFFFFFFFFFFC800000000000000001BFFFFFFFFFFFFFFFFF8000000000000000001", ptr: new(*big.Int), value: veryVeryBigInt},
 	{input: "10", ptr: new(big.Int), value: *big.NewInt(16)}, // non-pointer also works
+
+	// big int errors
 	{input: "C0", ptr: new(*big.Int), error: "rlp: expected input string or byte for *big.Int"},
 	{input: "00", ptr: new(*big.Int), error: "rlp: non-canonical integer (leading zero bytes) for *big.Int"},
 	{input: "820001", ptr: new(*big.Int), error: "rlp: non-canonical integer (leading zero bytes) for *big.Int"},
 	{input: "8105", ptr: new(*big.Int), error: "rlp: non-canonical size information for *big.Int"},
 
+	// uint256
+	{input: "80", ptr: new(*uint256.Int), value: uint256.NewInt(0)},
+	{input: "01", ptr: new(*uint256.Int), value: uint256.NewInt(1)},
+	{input: "88FFFFFFFFFFFFFFFF", ptr: new(*uint256.Int), value: uint256.NewInt(math.MaxUint64)},
+	{input: "89FFFFFFFFFFFFFFFFFF", ptr: new(*uint256.Int), value: veryBigInt256},
+	{input: "10", ptr: new(uint256.Int), value: *uint256.NewInt(16)}, // non-pointer also works
+
+	// uint256 errors
+	{input: "C0", ptr: new(*uint256.Int), error: "rlp: expected input string or byte for *uint256.Int"},
+	{input: "00", ptr: new(*uint256.Int), error: "rlp: non-canonical integer (leading zero bytes) for *uint256.Int"},
+	{input: "820001", ptr: new(*uint256.Int), error: "rlp: non-canonical integer (leading zero bytes) for *uint256.Int"},
+	{input: "8105", ptr: new(*uint256.Int), error: "rlp: non-canonical size information for *uint256.Int"},
+	{input: "A1FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFF00", ptr: new(*uint256.Int), error: "rlp: value too large for uint256"},
+
 	// structs
 	{
 		input: "C50583343434",
@@ -1223,6 +1244,27 @@ func BenchmarkDecodeBigInts(b *testing.B) {
 	}
 }
 
+func BenchmarkDecodeU256Ints(b *testing.B) {
+	ints := make([]*uint256.Int, 200)
+	for i := range ints {
+		ints[i], _ = uint256.FromBig(math.BigPow(2, int64(i)))
+	}
+	enc, err := EncodeToBytes(ints)
+	if err != nil {
+		b.Fatal(err)
+	}
+	b.SetBytes(int64(len(enc)))
+	b.ReportAllocs()
+	b.ResetTimer()
+
+	var out []*uint256.Int
+	for i := 0; i < b.N; i++ {
+		if err := DecodeBytes(enc, &out); err != nil {
+			b.Fatal(err)
+		}
+	}
+}
+
 func encodeTestSlice(n uint) []byte {
 	s := make([]uint, n)
 	for i := uint(0); i < n; i++ {
diff --git a/rlp/encbuffer.go b/rlp/encbuffer.go
index d2c6d93bc..9ac4fcb2c 100644
--- a/rlp/encbuffer.go
+++ b/rlp/encbuffer.go
@@ -17,10 +17,13 @@
 package rlp
 
 import (
+	"encoding/binary"
 	"io"
 	"math/big"
 	"reflect"
 	"sync"
+
+	"github.com/holiman/uint256"
 )
 
 type encBuffer struct {
@@ -169,6 +172,23 @@ func (w *encBuffer) writeBigInt(i *big.Int) {
 	}
 }
 
+// writeUint256 writes z as an integer.
+func (w *encBuffer) writeUint256(z *uint256.Int) {
+	bitlen := z.BitLen()
+	if bitlen <= 64 {
+		w.writeUint64(z.Uint64())
+		return
+	}
+	nBytes := byte((bitlen + 7) / 8)
+	var b [33]byte
+	binary.BigEndian.PutUint64(b[1:9], z[3])
+	binary.BigEndian.PutUint64(b[9:17], z[2])
+	binary.BigEndian.PutUint64(b[17:25], z[1])
+	binary.BigEndian.PutUint64(b[25:33], z[0])
+	b[32-nBytes] = 0x80 + nBytes
+	w.str = append(w.str, b[32-nBytes:]...)
+}
+
 // list adds a new list header to the header stack. It returns the index of the header.
 // Call listEnd with this index after encoding the content of the list.
 func (buf *encBuffer) list() int {
@@ -376,6 +396,11 @@ func (w EncoderBuffer) WriteBigInt(i *big.Int) {
 	w.buf.writeBigInt(i)
 }
 
+// WriteUint256 encodes uint256.Int as an RLP string.
+func (w EncoderBuffer) WriteUint256(i *uint256.Int) {
+	w.buf.writeUint256(i)
+}
+
 // WriteBytes encodes b as an RLP string.
 func (w EncoderBuffer) WriteBytes(b []byte) {
 	w.buf.writeBytes(b)
diff --git a/rlp/encode.go b/rlp/encode.go
index a377a1ef4..3fac0bd2d 100644
--- a/rlp/encode.go
+++ b/rlp/encode.go
@@ -24,6 +24,7 @@ import (
 	"reflect"
 
 	"github.com/ethereum/go-ethereum/rlp/internal/rlpstruct"
+	"github.com/holiman/uint256"
 )
 
 var (
@@ -144,6 +145,10 @@ func makeWriter(typ reflect.Type, ts rlpstruct.Tags) (writer, error) {
 		return writeBigIntPtr, nil
 	case typ.AssignableTo(bigInt):
 		return writeBigIntNoPtr, nil
+	case typ == reflect.PtrTo(u256Int):
+		return writeU256IntPtr, nil
+	case typ == u256Int:
+		return writeU256IntNoPtr, nil
 	case kind == reflect.Ptr:
 		return makePtrWriter(typ, ts)
 	case reflect.PtrTo(typ).Implements(encoderInterface):
@@ -206,6 +211,22 @@ func writeBigIntNoPtr(val reflect.Value, w *encBuffer) error {
 	return nil
 }
 
+func writeU256IntPtr(val reflect.Value, w *encBuffer) error {
+	ptr := val.Interface().(*uint256.Int)
+	if ptr == nil {
+		w.str = append(w.str, 0x80)
+		return nil
+	}
+	w.writeUint256(ptr)
+	return nil
+}
+
+func writeU256IntNoPtr(val reflect.Value, w *encBuffer) error {
+	i := val.Interface().(uint256.Int)
+	w.writeUint256(&i)
+	return nil
+}
+
 func writeBytes(val reflect.Value, w *encBuffer) error {
 	w.writeBytes(val.Bytes())
 	return nil
diff --git a/rlp/encode_test.go b/rlp/encode_test.go
index 82c490a80..02be47d0e 100644
--- a/rlp/encode_test.go
+++ b/rlp/encode_test.go
@@ -27,6 +27,7 @@ import (
 	"testing"
 
 	"github.com/ethereum/go-ethereum/common/math"
+	"github.com/holiman/uint256"
 )
 
 type testEncoder struct {
@@ -147,6 +148,30 @@ var encTests = []encTest{
 	{val: big.NewInt(-1), error: "rlp: cannot encode negative big.Int"},
 	{val: *big.NewInt(-1), error: "rlp: cannot encode negative big.Int"},
 
+	// uint256
+	{val: uint256.NewInt(0), output: "80"},
+	{val: uint256.NewInt(1), output: "01"},
+	{val: uint256.NewInt(127), output: "7F"},
+	{val: uint256.NewInt(128), output: "8180"},
+	{val: uint256.NewInt(256), output: "820100"},
+	{val: uint256.NewInt(1024), output: "820400"},
+	{val: uint256.NewInt(0xFFFFFF), output: "83FFFFFF"},
+	{val: uint256.NewInt(0xFFFFFFFF), output: "84FFFFFFFF"},
+	{val: uint256.NewInt(0xFFFFFFFFFF), output: "85FFFFFFFFFF"},
+	{val: uint256.NewInt(0xFFFFFFFFFFFF), output: "86FFFFFFFFFFFF"},
+	{val: uint256.NewInt(0xFFFFFFFFFFFFFF), output: "87FFFFFFFFFFFFFF"},
+	{
+		val:    new(uint256.Int).SetBytes(unhex("102030405060708090A0B0C0D0E0F2")),
+		output: "8F102030405060708090A0B0C0D0E0F2",
+	},
+	{
+		val:    new(uint256.Int).SetBytes(unhex("0100020003000400050006000700080009000A000B000C000D000E01")),
+		output: "9C0100020003000400050006000700080009000A000B000C000D000E01",
+	},
+	// non-pointer uint256.Int
+	{val: *uint256.NewInt(0), output: "80"},
+	{val: *uint256.NewInt(0xFFFFFF), output: "83FFFFFF"},
+
 	// byte arrays
 	{val: [0]byte{}, output: "80"},
 	{val: [1]byte{0}, output: "00"},
@@ -256,6 +281,12 @@ var encTests = []encTest{
 		output: "F90200CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376CF84617364668471776572847A786376",
 	},
 
+	// Non-byte arrays are encoded as lists.
+	// Note that it is important to test [4]uint64 specifically,
+	// because that's the underlying type of uint256.Int.
+	{val: [4]uint32{1, 2, 3, 4}, output: "C401020304"},
+	{val: [4]uint64{1, 2, 3, 4}, output: "C401020304"},
+
 	// RawValue
 	{val: RawValue(unhex("01")), output: "01"},
 	{val: RawValue(unhex("82FFFF")), output: "82FFFF"},
@@ -301,6 +332,7 @@ var encTests = []encTest{
 	{val: (*[]byte)(nil), output: "80"},
 	{val: (*[10]byte)(nil), output: "80"},
 	{val: (*big.Int)(nil), output: "80"},
+	{val: (*uint256.Int)(nil), output: "80"},
 	{val: (*[]string)(nil), output: "C0"},
 	{val: (*[10]string)(nil), output: "C0"},
 	{val: (*[]interface{})(nil), output: "C0"},
@@ -509,6 +541,23 @@ func BenchmarkEncodeBigInts(b *testing.B) {
 	}
 }
 
+func BenchmarkEncodeU256Ints(b *testing.B) {
+	ints := make([]*uint256.Int, 200)
+	for i := range ints {
+		ints[i], _ = uint256.FromBig(math.BigPow(2, int64(i)))
+	}
+	out := bytes.NewBuffer(make([]byte, 0, 4096))
+	b.ResetTimer()
+	b.ReportAllocs()
+
+	for i := 0; i < b.N; i++ {
+		out.Reset()
+		if err := Encode(out, ints); err != nil {
+			b.Fatal(err)
+		}
+	}
+}
+
 func BenchmarkEncodeConcurrentInterface(b *testing.B) {
 	type struct1 struct {
 		A string
diff --git a/rlp/rlpgen/gen.go b/rlp/rlpgen/gen.go
index 1deb5a93c..0c6586482 100644
--- a/rlp/rlpgen/gen.go
+++ b/rlp/rlpgen/gen.go
@@ -283,7 +283,7 @@ func (op byteArrayOp) genDecode(ctx *genContext) (string, string) {
 	return resultV, b.String()
 }
 
-// bigIntNoPtrOp handles non-pointer big.Int.
+// bigIntOp handles big.Int.
 // This exists because big.Int has it's own decoder operation on rlp.Stream,
 // but the decode method returns *big.Int, so it needs to be dereferenced.
 type bigIntOp struct {
@@ -330,6 +330,49 @@ func (op bigIntOp) genDecode(ctx *genContext) (string, string) {
 	return result, b.String()
 }
 
+// uint256Op handles "github.com/holiman/uint256".Int
+type uint256Op struct {
+	pointer bool
+}
+
+func (op uint256Op) genWrite(ctx *genContext, v string) string {
+	var b bytes.Buffer
+
+	dst := v
+	if !op.pointer {
+		dst = "&" + v
+	}
+	fmt.Fprintf(&b, "w.WriteUint256(%s)\n", dst)
+
+	// Wrap with nil check.
+	if op.pointer {
+		code := b.String()
+		b.Reset()
+		fmt.Fprintf(&b, "if %s == nil {\n", v)
+		fmt.Fprintf(&b, "  w.Write(rlp.EmptyString)")
+		fmt.Fprintf(&b, "} else {\n")
+		fmt.Fprint(&b, code)
+		fmt.Fprintf(&b, "}\n")
+	}
+
+	return b.String()
+}
+
+func (op uint256Op) genDecode(ctx *genContext) (string, string) {
+	ctx.addImport("github.com/holiman/uint256")
+
+	var b bytes.Buffer
+	resultV := ctx.temp()
+	fmt.Fprintf(&b, "var %s uint256.Int\n", resultV)
+	fmt.Fprintf(&b, "if err := dec.ReadUint256(&%s); err != nil { return err }\n", resultV)
+
+	result := resultV
+	if op.pointer {
+		result = "&" + resultV
+	}
+	return result, b.String()
+}
+
 // encoderDecoderOp handles rlp.Encoder and rlp.Decoder.
 // In order to be used with this, the type must implement both interfaces.
 // This restriction may be lifted in the future by creating separate ops for
@@ -635,6 +678,9 @@ func (bctx *buildContext) makeOp(name *types.Named, typ types.Type, tags rlpstru
 		if isBigInt(typ) {
 			return bigIntOp{}, nil
 		}
+		if isUint256(typ) {
+			return uint256Op{}, nil
+		}
 		if typ == bctx.rawValueType {
 			return bctx.makeRawValueOp(), nil
 		}
@@ -647,6 +693,9 @@ func (bctx *buildContext) makeOp(name *types.Named, typ types.Type, tags rlpstru
 		if isBigInt(typ.Elem()) {
 			return bigIntOp{pointer: true}, nil
 		}
+		if isUint256(typ.Elem()) {
+			return uint256Op{pointer: true}, nil
+		}
 		// Encoder/Decoder interfaces.
 		if bctx.isEncoder(typ) {
 			if bctx.isDecoder(typ) {
diff --git a/rlp/rlpgen/gen_test.go b/rlp/rlpgen/gen_test.go
index 241c34b6d..ff3b8385a 100644
--- a/rlp/rlpgen/gen_test.go
+++ b/rlp/rlpgen/gen_test.go
@@ -47,7 +47,7 @@ func init() {
 	}
 }
 
-var tests = []string{"uints", "nil", "rawvalue", "optional", "bigint"}
+var tests = []string{"uints", "nil", "rawvalue", "optional", "bigint", "uint256"}
 
 func TestOutput(t *testing.T) {
 	for _, test := range tests {
diff --git a/rlp/rlpgen/testdata/uint256.in.txt b/rlp/rlpgen/testdata/uint256.in.txt
new file mode 100644
index 000000000..ed16e0a78
--- /dev/null
+++ b/rlp/rlpgen/testdata/uint256.in.txt
@@ -0,0 +1,10 @@
+// -*- mode: go -*-
+
+package test
+
+import "github.com/holiman/uint256"
+
+type Test struct {
+	Int      *uint256.Int
+	IntNoPtr uint256.Int
+}
diff --git a/rlp/rlpgen/testdata/uint256.out.txt b/rlp/rlpgen/testdata/uint256.out.txt
new file mode 100644
index 000000000..5e6d3ed99
--- /dev/null
+++ b/rlp/rlpgen/testdata/uint256.out.txt
@@ -0,0 +1,44 @@
+package test
+
+import "github.com/ethereum/go-ethereum/rlp"
+import "github.com/holiman/uint256"
+import "io"
+
+func (obj *Test) EncodeRLP(_w io.Writer) error {
+	w := rlp.NewEncoderBuffer(_w)
+	_tmp0 := w.List()
+	if obj.Int == nil {
+		w.Write(rlp.EmptyString)
+	} else {
+		w.WriteUint256(obj.Int)
+	}
+	w.WriteUint256(&obj.IntNoPtr)
+	w.ListEnd(_tmp0)
+	return w.Flush()
+}
+
+func (obj *Test) DecodeRLP(dec *rlp.Stream) error {
+	var _tmp0 Test
+	{
+		if _, err := dec.List(); err != nil {
+			return err
+		}
+		// Int:
+		var _tmp1 uint256.Int
+		if err := dec.ReadUint256(&_tmp1); err != nil {
+			return err
+		}
+		_tmp0.Int = &_tmp1
+		// IntNoPtr:
+		var _tmp2 uint256.Int
+		if err := dec.ReadUint256(&_tmp2); err != nil {
+			return err
+		}
+		_tmp0.IntNoPtr = _tmp2
+		if err := dec.ListEnd(); err != nil {
+			return err
+		}
+	}
+	*obj = _tmp0
+	return nil
+}
diff --git a/rlp/rlpgen/types.go b/rlp/rlpgen/types.go
index 19694262e..ea7dc96d8 100644
--- a/rlp/rlpgen/types.go
+++ b/rlp/rlpgen/types.go
@@ -97,6 +97,16 @@ func isBigInt(typ types.Type) bool {
 	return name.Pkg().Path() == "math/big" && name.Name() == "Int"
 }
 
+// isUint256 checks whether 'typ' is "github.com/holiman/uint256".Int.
+func isUint256(typ types.Type) bool {
+	named, ok := typ.(*types.Named)
+	if !ok {
+		return false
+	}
+	name := named.Obj()
+	return name.Pkg().Path() == "github.com/holiman/uint256" && name.Name() == "Int"
+}
+
 // isByte checks whether the underlying type of 'typ' is uint8.
 func isByte(typ types.Type) bool {
 	basic, ok := resolveUnderlying(typ).(*types.Basic)