diff --git a/compiler-rt/lib/fuzzer/FuzzerMutate.cpp b/compiler-rt/lib/fuzzer/FuzzerMutate.cpp
--- a/compiler-rt/lib/fuzzer/FuzzerMutate.cpp
+++ b/compiler-rt/lib/fuzzer/FuzzerMutate.cpp
@@ -69,6 +69,10 @@
 
 size_t MutationDispatcher::Mutate_Custom(uint8_t *Data, size_t Size,
                                          size_t MaxSize) {
+  if (EF->__msan_unpoison)
+    EF->__msan_unpoison(Data, Size);
+  if (EF->__msan_unpoison_param)
+    EF->__msan_unpoison_param(4);
   return EF->LLVMFuzzerCustomMutator(Data, Size, MaxSize,
                                      Rand.Rand<unsigned int>());
 }
@@ -83,9 +87,18 @@
     return 0;
   CustomCrossOverInPlaceHere.resize(MaxSize);
   auto &U = CustomCrossOverInPlaceHere;
+
+  if (EF->__msan_unpoison) {
+    EF->__msan_unpoison(Data, Size);
+    EF->__msan_unpoison(Other.data(), Other.size());
+    EF->__msan_unpoison(U.data(), U.size());
+  }
+  if (EF->__msan_unpoison_param)
+    EF->__msan_unpoison_param(7);
   size_t NewSize = EF->LLVMFuzzerCustomCrossOver(
       Data, Size, Other.data(), Other.size(), U.data(), U.size(),
       Rand.Rand<unsigned int>());
+
   if (!NewSize)
     return 0;
   assert(NewSize <= MaxSize && "CustomCrossOver returned overisized unit");
diff --git a/compiler-rt/test/fuzzer/MsanCustomMutator.cpp b/compiler-rt/test/fuzzer/MsanCustomMutator.cpp
new file mode 100644
--- /dev/null
+++ b/compiler-rt/test/fuzzer/MsanCustomMutator.cpp
@@ -0,0 +1,47 @@
+// Part of the LLVM Project, under the Apache License v2.0 with LLVM Exceptions.
+// See https://llvm.org/LICENSE.txt for license information.
+// SPDX-License-Identifier: Apache-2.0 WITH LLVM-exception
+
+// Triggers the bug described here:
+// https://github.com/google/oss-fuzz/issues/4605
+//
+// Tests that custom mutators do not cause MSan false positives.  We are careful
+// to use every parameter to ensure none cause false positives.
+
+#include <algorithm>
+#include <cstddef>
+#include <cstdint>
+#include <cstdio>
+#include <cstring>
+
+extern "C" {
+
+int LLVMFuzzerTestOneInput(const uint8_t *Data, size_t Size) { return 0; }
+
+size_t LLVMFuzzerCustomMutator(uint8_t *Data, size_t Size, size_t MaxSize,
+                               unsigned int Seed) {
+  if (Seed == 7)
+    return 0;
+  if (MaxSize == 0)
+    return 0;
+  for (size_t I = 0; I < Size; ++I) {
+    if (Data[I] == 42) {
+      printf("BINGO\n");
+    }
+  }
+  return Size;
+}
+
+size_t LLVMFuzzerCustomCrossOver(
+    const uint8_t *Data1, size_t Size1, const uint8_t *Data2, size_t Size2,
+    uint8_t *Out, size_t MaxOutSize, unsigned int Seed) {
+  if (Seed == 7)
+    return 0;
+  size_t I = 0;
+  for (; I < Size1 && I < Size2 && I < MaxOutSize; ++I) {
+    Out[I] = std::min(Data1[I], Data2[I]);
+  }
+  return I;
+}
+
+} // extern "C"
diff --git a/compiler-rt/test/fuzzer/msan-custom-mutator.test b/compiler-rt/test/fuzzer/msan-custom-mutator.test
new file mode 100644
--- /dev/null
+++ b/compiler-rt/test/fuzzer/msan-custom-mutator.test
@@ -0,0 +1,5 @@
+REQUIRES: msan
+RUN: %msan_compiler %S/MsanCustomMutator.cpp -o %t
+RUN: %run %t -seed=1 -runs=1000 2>&1 | FileCheck %s
+
+CHECK-NOT: MemorySanitizer: use-of-uninitialized-value