Index: Objects/setobject.c
===================================================================
--- Objects/setobject.c	(revision 81048)
+++ Objects/setobject.c	(working copy)
@@ -1612,7 +1612,10 @@
 static PyObject *
 set_isub(PySetObject *so, PyObject *other)
 {
-    if (!PyAnySet_Check(other)) {
+    if (!PyAnySet_Check(other) ||
+	/* Fall back to s = s - o if len(s) < len(o) to
+	   avoid interation over a large set. */
+	PySet_GET_SIZE(so) < PySet_GET_SIZE(other)) {
         Py_INCREF(Py_NotImplemented);
         return Py_NotImplemented;
     }