diff --git a/Lib/test/test_pdb.py b/Lib/test/test_pdb.py
--- a/Lib/test/test_pdb.py
+++ b/Lib/test/test_pdb.py
@@ -552,6 +552,37 @@
     """
 
 
+def test_issue16653():
+    """Test that a destructor is traced when dereferenced by a local variable.
+
+    >>> class C:
+    ...     def __del__(self):
+    ...         x = 1
+
+    >>> def test_function():
+    ...     c = C()
+    ...     import pdb; pdb.Pdb(nosigint=True).set_trace()
+    ...     c = 1
+
+    >>> with PdbTestInput([
+    ...     'step',
+    ...     'step',
+    ...     'continue',
+    ... ]):
+    ...    test_function()
+    > <doctest test.test_pdb.test_issue16653[1]>(4)test_function()
+    -> c = 1
+    (Pdb) step
+    --Call--
+    > <doctest test.test_pdb.test_issue16653[0]>(2)__del__()
+    -> def __del__(self):
+    (Pdb) step
+    > <doctest test.test_pdb.test_issue16653[0]>(3)__del__()
+    -> x = 1
+    (Pdb) continue
+    """
+
+
 def pdb_invoke(method, arg):
     """Run pdb.method(arg)."""
     import pdb
diff --git a/Python/ceval.c b/Python/ceval.c
--- a/Python/ceval.c
+++ b/Python/ceval.c
@@ -3841,12 +3841,7 @@
     int result;
     if (tstate->tracing)
         return 0;
-    tstate->tracing++;
-    tstate->use_tracing = 0;
     result = func(obj, frame, what, arg);
-    tstate->use_tracing = ((tstate->c_tracefunc != NULL)
-                           || (tstate->c_profilefunc != NULL));
-    tstate->tracing--;
     return result;
 }
 
diff --git a/Python/sysmodule.c b/Python/sysmodule.c
--- a/Python/sysmodule.c
+++ b/Python/sysmodule.c
@@ -329,12 +329,13 @@
 
 
 static PyObject *
-call_trampoline(PyThreadState *tstate, PyObject* callback,
+call_trampoline(PyThreadState *tstate, PyObject* callback, int istrace,
                 PyFrameObject *frame, int what, PyObject *arg)
 {
     PyObject *args = PyTuple_New(3);
     PyObject *whatstr;
     PyObject *result;
+    Py_tracefunc tracefunc;
 
     if (args == NULL)
         return NULL;
@@ -348,12 +349,29 @@
     PyTuple_SET_ITEM(args, 1, whatstr);
     PyTuple_SET_ITEM(args, 2, arg);
 
-    /* call the Python-level function */
     PyFrame_FastToLocals(frame);
-    result = PyEval_CallObject(callback, args);
-    PyFrame_LocalsToFast(frame, 1);
-    if (result == NULL)
-        PyTraceBack_Here(frame);
+
+    /* Do no call the Python-level function when a destructor has been
+       traced/profiled in the call to PyFrame_FastToLocals and the
+       trace/profile function has been set to None from within the
+       corresponding Python-level function. */
+    tracefunc = istrace ? tstate->c_tracefunc : tstate->c_profilefunc;
+    if (tracefunc == NULL) {
+        result = Py_None;
+        Py_INCREF(Py_None);
+    }
+    else {
+        /* call the Python-level function */
+        tstate->tracing++;
+        tstate->use_tracing = 0;
+        result = PyEval_CallObject(callback, args);
+        PyFrame_LocalsToFast(frame, 1);
+        if (result == NULL)
+            PyTraceBack_Here(frame);
+        tstate->use_tracing = ((tstate->c_tracefunc != NULL)
+                               || (tstate->c_profilefunc != NULL));
+        tstate->tracing--;
+    }
 
     /* cleanup */
     Py_DECREF(args);
@@ -369,7 +387,7 @@
 
     if (arg == NULL)
         arg = Py_None;
-    result = call_trampoline(tstate, self, frame, what, arg);
+    result = call_trampoline(tstate, self, 0, frame, what, arg);
     if (result == NULL) {
         PyEval_SetProfile(NULL, NULL);
         return -1;
@@ -392,7 +410,7 @@
         callback = frame->f_trace;
     if (callback == NULL)
         return 0;
-    result = call_trampoline(tstate, callback, frame, what, arg);
+    result = call_trampoline(tstate, callback, 1, frame, what, arg);
     if (result == NULL) {
         PyEval_SetTrace(NULL, NULL);
         Py_XDECREF(frame->f_trace);