Analgesic effects of pellet implantation of the opiate antagonists naloxone and naltrexone and of chronic administration of naloxone by subcutaneous injection were examined. Rats were implanted with a slow-release pellet containing 10 mg naloxone or 10 mg naltrexone and tested for paw-lick latency on a hotplate apparatus. Controls were implanted with placebo pellets or given saline injections as appropriate. There were five test trials at intervals up to 72 h after implantation of naloxone and up to 120 h after the implantation of naltrexone. In a separate experiment, 5 mg/kg naloxone was injected; there were single trials on 5 consecutive days. All drug-treated animals displayed clear and substantial analgesia by their second test trial. This "paradoxical" analgesia was gradually reversed in the pellet-implant groups as tissue levels of the antagonists declined, but increased progressively with each trial involving injections. It was hypothesized that blockade of endogenous opiates by antagonists resulted in a form of "super-pain" on the hotplate, which in turn activated a normally redundant "backup" analgesic system. The results with naloxone injections show that unlike opiate-mediated analgesia, this hypothetical system is resistant to tolerance.