Experimental data show that opiates interfere with calcium influx in the cell and that some calcium-channel blockers are analgesic. We therefore studied the effect of the calcium-receptor blocker nifedipine on the analgesic effect of morphine in the rat, using tail-flick responses, and in humans, using measurements of the intensity of postoperative pain. In both the experimental animals and humans nifedipine significantly (P less than 0.001) increased the analgesic effect of morphine independently of any effect on the metabolism of morphine. Respiratory and cardiovascular functions were not significantly changed by nifedipine. The data indicate that Ca2+ is important in mediating the analgesic effects of opiates and suggest that calcium-receptor blockers might find a place in the treatment of pain.