Under certain experimental and clinical conditions, opioid antagonists have been demonstrated to have analgesic properties. In this open-label, nonrandomized, within-subject comparison, the effect of chronic treatment with the antagonist, naltrexone, on tolerance for experimental pain was evaluated in a small sample of male opioid addicts (N = 10) receiving naltrexone maintenance. Cold-pressor pain tolerance was measured during (> or = 6 weeks) and after discontinuation (> or = 1 week) of naltrexone treatment. Intra-subject comparison revealed that eight of the ten subjects were more pain tolerant (median + 20 sec) while receiving naltrexone. It is suggested that either midbrain opioid system upregulation in the presence of naltrexone or underlying individual differences in pain tolerance in persons with addictive disease provide potential explanations for these findings.