We evaluated the effects of s.c. administration of naloxone in mice with streptozotocin-induced diabetes, compared to those in age-matched naive mice. Naloxone injected s.c. produced a dose-related increase in tail-flick latency in diabetic mice but not in naive mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole, a selective antagonist of delta-opioid receptors. These results indicate that naloxone-induced 'paradoxical' analgesia in diabetic mice may be mediated by delta-opioid receptors.