Chronic treatment of rats with naloxone for 5 days increased the analgesic threshold (hot plate latency). Further, when rats were treated with morphine-admixed food for 3 days after the chronic naloxone treatment the withdrawal signs precipitated by naloxone were significantly greater in the naloxone-pretreated rats than in saline-pretreated rats. These results suggest that paradoxical analgesia and enhancement of the morphine withdrawal signs induced by chronic naloxone treatment may be associated mainly with up-regulation of mu- and delta-opioid binding sites in the central nervous system.