diff --git a/Lib/ctypes/__init__.py b/Lib/ctypes/__init__.py
--- a/Lib/ctypes/__init__.py
+++ b/Lib/ctypes/__init__.py
@@ -265,7 +265,21 @@ class c_wchar_p(_SimpleCData):
 class c_wchar(_SimpleCData):
     _type_ = "u"
 
-POINTER(c_wchar).from_param = c_wchar_p.from_param #_SimpleCData.c_wchar_p_from_param
+def _reset_cache():
+    _pointer_type_cache.clear()
+    _c_functype_cache.clear()
+    if _os.name in ("nt", "ce"):
+        _win_functype_cache.clear()
+    # _SimpleCData.c_wchar_p_from_param
+    POINTER(c_wchar).from_param = c_wchar_p.from_param
+    # _SimpleCData.c_char_p_from_param
+    POINTER(c_char).from_param = c_char_p.from_param
+    _pointer_type_cache[None] = c_void_p
+    # XXX for whatever reasons, creating the first instance of a callback
+    # function is needed for the unittests on Win64 to succeed.  This MAY
+    # be a compiler bug, since the problem occurs only when _ctypes is
+    # compiled with the MS SDK compiler.  Or an uninitialized variable?
+    CFUNCTYPE(c_int)(lambda: None)
 
 def create_unicode_buffer(init, size=None):
     """create_unicode_buffer(aString) -> character array
@@ -285,7 +299,6 @@ def create_unicode_buffer(init, size=Non
         return buf
     raise TypeError(init)
 
-POINTER(c_char).from_param = c_char_p.from_param #_SimpleCData.c_char_p_from_param
 
 # XXX Deprecated
 def SetPointerType(pointer, cls):
@@ -445,8 +458,6 @@ if _os.name in ("nt", "ce"):
             descr = FormatError(code).strip()
         return WindowsError(code, descr)
 
-_pointer_type_cache[None] = c_void_p
-
 if sizeof(c_uint) == sizeof(c_void_p):
     c_size_t = c_uint
     c_ssize_t = c_int
@@ -534,3 +545,5 @@ del(kind)
 # be a compiler bug, since the problem occurs only when _ctypes is
 # compiled with the MS SDK compiler.  Or an uninitialized variable?
 CFUNCTYPE(c_int)(lambda: None)
+
+_reset_cache()
diff --git a/Lib/ctypes/test/test_as_parameter.py b/Lib/ctypes/test/test_as_parameter.py
--- a/Lib/ctypes/test/test_as_parameter.py
+++ b/Lib/ctypes/test/test_as_parameter.py
@@ -74,6 +74,7 @@ class BasicWrapTestCase(unittest.TestCas
     def test_callbacks(self):
         f = dll._testfunc_callback_i_if
         f.restype = c_int
+        f.argtypes = None
 
         MyCallback = CFUNCTYPE(c_int, c_int)
 
diff --git a/Lib/ctypes/test/test_functions.py b/Lib/ctypes/test/test_functions.py
--- a/Lib/ctypes/test/test_functions.py
+++ b/Lib/ctypes/test/test_functions.py
@@ -250,6 +250,7 @@ class FunctionTestCase(unittest.TestCase
     def test_callbacks(self):
         f = dll._testfunc_callback_i_if
         f.restype = c_int
+        f.argtypes = None
 
         MyCallback = CFUNCTYPE(c_int, c_int)
 
diff --git a/Lib/test/regrtest.py b/Lib/test/regrtest.py
--- a/Lib/test/regrtest.py
+++ b/Lib/test/regrtest.py
@@ -1350,6 +1350,7 @@ def dash_R_cleanup(fs, ps, pic, zdc, abc
     import _strptime, linecache
     import urllib.parse, urllib.request, mimetypes, doctest
     import struct, filecmp, collections.abc
+    import ctypes
     from distutils.dir_util import _path_created
     from weakref import WeakSet
 
@@ -1401,6 +1402,7 @@ def dash_R_cleanup(fs, ps, pic, zdc, abc
     filecmp._cache.clear()
     struct._clearcache()
     doctest.master = None
+    ctypes._reset_cache()
 
     # Collect cyclic trash.
     gc.collect()