Reproductive adult male and female deer mice that received daily (7 days) injections of either the prototypic exogenous opiate antagonist, naloxone (1.0 mg/kg), or the endogenous putative antiopioid tetrapeptide, Tyr-MIF-1 (Tyr-Pro-Leu-Gly amide; 1.0 and 10 mg/kg), followed by determinations of thermal nociceptive sensitivity (hot-plate response) developed hypoalgesia. There were significant sex differences in this opioid blockade-induced or associated analgesia, with male mice displaying significantly greater hypoalgesia than females. Mice that received daily injections of either naloxone or Tyr-MIF-1 for 7 days without any accompanying determinations of nociceptive sensitivity (days 2-6 of treatment) failed to show any hypoalgesia on day 7 when they received the antagonist followed by a measurement of nociception. These results indicate that there are sex differences in both naloxone- and Tyr-MIF-1-induced hypoalgesia, and suggest that this pattern may be associated with sexually dimorphic opioid modulation of aversive conditioning.