The interaction with nitrous oxide analgesia of drugs that act at the benzodiazepine receptor was evaluated in the rat tail flick model. Nitrous oxide produced dose-related analgesia, which was potentiated by diazepam, a benzodiazepine agonist, antagonized by noreleagnine, a benzodiazepine inverse agonist. Pretreatment with the benzodiazepine antagonist Ro 15-1788 blocked the effects of both diazepam and noreleagnine on nitrous oxide analgesia. Subanesthetic doses of sodium pentobarbital and chloral hydrate produced nonsignificant trends to reduce the analgesic action of nitrous oxide. These data provide evidence for the presence of specific benzodiazepine receptors capable of modulating the analgesic effect of nitrous oxide.