Opioid and nonopioid mediated changes in pain sensitivity have been observed after exposure to various stressful conditions. A series of inescapable shocks sequentially produces an early form of analgesia which is not affected by the opiate antagonist, naltrexone, and a late antinociceptive response which is sensitive to reversal by naltrexone. Here, this is shown to be true over a wide range of doses. In a further experiment subjects given either escapable or inescapable shock were analgesic immediately after the stress session. However, the analgesia of inescapably shocked subjects was more sensitive to reversal by naltrexone. A final experiment revealed that inescapably shocked subjects, but not escapably shocked subjects, were hyperreactive to the analgesic effects of morphine 24 hr after shock. These results suggest that activation of an opiate system occurs only after extended exposure to stress and that this activation is greater when the stress is inescapable. Implications for opioid versus nonopioid mechanisms of stress-induced analgesia are discussed.