The behavioral consequences of exposure to stressors such as inescapable shock are usually transitory if testing is conducted in an environment different from that in which the stressor was administered. The behaviors tested have generally been motivated by discrete stimuli in the environment (e.g., activity in reaction to shock) or have been part of homeostatic regulatory mechanisms (e.g., eating). Here we investigated the effects of inescapable shock on a behavior that is not so tightly tied to motivating and reinforcing conditions, daily activity in a familiar home cage/running wheel environment. Rats lived in the wheel environment for 44-85 days before treatment. Inescapable shock produced only a transient reduction of water intake and body weight, but daily running was depressed for 14-42 days (the maximum period studied) depending on the conditions. This long-term effect on activity occurred despite the fact that shock was administered in an environment very different from the animal's home running wheel environment. The activity reduction was reversed by desipramine in a dose dependent fashion. Indeed, the activity of inescapably shocked animals treated with the optimum dose of desipramine exceeded that of control animals undergoing neither stress nor drug treatment. The maximum effect of desipramine required 7 days of treatment. Desipramine did not affect the activity of control subjects.