The effect of chronic stress on analgesic responsiveness to morphine was studied in mature rats of different ages. Chronic stress consisted of eighteen 10-sec exposures (three/min) in 2 degrees C water for 54 consecutive days. From day 20, at 4-day intervals, the rats were not stressed but instead given i.p. injections of, sequentially: 10, 0 (saline), 5, (2 mg/kg of naltrexone) + 10, 2.5, 1, 20 and 10 mg/kg of morphine sulfate. On these days, tail-flick latencies were measured before and 5, 10, 15, 30, 60, 120 and 180 min after morphine injection. The responsiveness to morphine was significantly altered by exposure to chronic stress in young, mature rats (4 months) as compared to control rats. A dose of 10 mg/kg of morphine induced a diphasic response. Initial increased tail-flick reflexes (at 5 min after injection) were followed by slight but nonsignificant decreased responses to the tail-flick test. At 30 min, the dose-response curve was shifted to the right. No alteration of the response to morphine was observed in older rats (15-17 months) exposed to chronic stress, unless they had been submitted to chronic stress at 4 months of age. In addition, the response after a second exposure to chronic stress to morphine was highly dependent on, and similar to, the age-dependent response after a first exposure. These results demonstrate that the endogenous opiate system can be altered by exposure to chronic stress even after maturation has occurred and that this alteration has long-term effects on the reactivity to morphine.