diff --git a/Lib/httplib.py b/Lib/httplib.py
--- a/Lib/httplib.py
+++ b/Lib/httplib.py
@@ -857,6 +857,8 @@ class HTTPConnection:
         if not url:
             url = '/'
         hdr = '%s %s %s' % (method, url, self._http_vsn_str)
+        if isinstance(hdr, unicode):
+            hdr = hdr.encode('ISO-8859-1')
 
         self._output(hdr)
 
@@ -932,7 +934,14 @@ class HTTPConnection:
         if self.__state != _CS_REQ_STARTED:
             raise CannotSendHeader()
 
-        hdr = '%s: %s' % (header, '\r\n\t'.join([str(v) for v in values]))
+        def encode_value(value):
+            if isinstance(value, unicode):
+                return value.encode('ISO-8859-1')
+            else:
+                return str(value)
+
+        values = '\r\n\t'.join(map(encode_value, values))
+        hdr = '%s: %s' % (header, values)
         self._output(hdr)
 
     def endheaders(self, message_body=None):
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
@@ -1318,6 +1318,16 @@ class RequestTests(unittest.TestCase):
         req = Request(url)
         self.assertEqual(req.get_full_url(), url)
 
+    def test_unicode_uri(self):
+        # Issue #12398
+        h = urllib2.AbstractHTTPHandler()
+        o = h.parent = MockOpener()
+        http = MockHTTPClass()
+        non_ascii = b'\xFF'
+        request = urllib2.Request(u'http://www.host\xe9.org/\xe0', data=non_ascii)
+        r = h.do_open(http, request)
+
+
 def test_main(verbose=None):
     from test import test_urllib2
     test_support.run_doctest(test_urllib2, verbose)