diff --git a/Lib/test/test_urllib2.py b/Lib/test/test_urllib2.py
--- a/Lib/test/test_urllib2.py
+++ b/Lib/test/test_urllib2.py
@@ -124,6 +124,19 @@
     >>> r.get_header("Not-there", "default")
     'default'
 
+    Method r.remove_header should remove items both from r.headers and
+    r.unredirected_hdrs dictionaries
+
+    >>> r.remove_header("Spam-eggs")
+    >>> r.has_header("Spam-eggs")
+    False
+    >>> r.add_unredirected_header("Unredirected-spam", "Eggs")
+    >>> r.has_header("Unredirected-spam")
+    True
+    >>> r.remove_header("Unredirected-spam")
+    >>> r.has_header("Unredirected-spam")
+    False
+
     """
 
 
@@ -1432,6 +1445,20 @@
         self.opener_has_handler(o, MyHTTPHandler)
         self.opener_has_handler(o, MyOtherHTTPHandler)
 
+    def test_issue16464(self):
+        opener = urllib.request.build_opener()
+        request = urllib.request.Request("http://www.python.org/~jeremy/")
+        self.assertEqual(None, request.data)
+
+        opener.open(request, "1".encode("us-ascii"))
+        self.assertEqual(b"1", request.data)
+        self.assertEqual("1", request.get_header("Content-length"))
+
+        opener.open(request, "1234567890".encode("us-ascii"))
+        self.assertEqual(b"1234567890", request.data)
+        self.assertEqual("10", request.get_header("Content-length"))
+
+
     def opener_has_handler(self, opener, handler_class):
         self.assertTrue(any(h.__class__ == handler_class
                             for h in opener.handlers))
@@ -1455,6 +1482,16 @@
         self.assertTrue(self.get.data)
         self.assertEqual("POST", self.get.get_method())
 
+    # issue 16464
+    # if we change data we need to remove content-length header
+    # (cause it's most probably calculated for previous value)
+    def test_setting_data_should_remove_content_length(self):
+        self.assertFalse("Content-length" in self.get.unredirected_hdrs)
+        self.get.add_unredirected_header("Content-length", 42)
+        self.assertEqual(42, self.get.unredirected_hdrs["Content-length"])
+        self.get.data = "spam"
+        self.assertFalse("Content-length" in self.get.unredirected_hdrs)
+
     def test_get_full_url(self):
         self.assertEqual("http://www.python.org/~jeremy/",
                          self.get.get_full_url())
diff --git a/Lib/urllib/request.py b/Lib/urllib/request.py
--- a/Lib/urllib/request.py
+++ b/Lib/urllib/request.py
@@ -265,12 +265,13 @@
         # unwrap('<URL:type://host/path>') --> 'type://host/path'
         self.full_url = unwrap(url)
         self.full_url, self.fragment = splittag(self.full_url)
+        self.headers = {}
+        self.unredirected_hdrs = {}
+        self._data = None
         self.data = data
-        self.headers = {}
         self._tunnel_host = None
         for key, value in headers.items():
             self.add_header(key, value)
-        self.unredirected_hdrs = {}
         if origin_req_host is None:
             origin_req_host = request_host(self)
         self.origin_req_host = origin_req_host
@@ -278,6 +279,23 @@
         self.method = method
         self._parse()
 
+    def _get_data(self):
+        return self._data
+
+    def _set_data(self, data):
+        if data != self._data:
+            # issue 16464
+            # if we change data we need to remove content-length header
+            # (cause it's most probably calculated for previous value)
+            self._data = data
+            if self.has_header("Content-length"):
+                self.remove_header("Content-length")
+
+    def _del_data(self):
+        self._data = None
+
+    data = property(_get_data, _set_data, _del_data)
+
     def _parse(self):
         self.type, rest = splittype(self.full_url)
         if self.type is None:
@@ -373,6 +391,12 @@
             header_name,
             self.unredirected_hdrs.get(header_name, default))
 
+    def remove_header(self, header_name):
+        if header_name in self.headers:
+            del self.headers[header_name]
+        elif header_name in self.unredirected_hdrs:
+            del self.unredirected_hdrs[header_name]
+
     def header_items(self):
         hdrs = self.unredirected_hdrs.copy()
         hdrs.update(self.headers)