Naloxone enhanced retention when systemically administered to male F344 rats after training in a one-trial inhibitory avoidance task. Further, the memory-enhancing ability of naloxone appears to be opiate receptor dependent, because it was antagonized by morphine. Naloxone also improved retention of rats in an active avoidance task, indicating that the effect of naloxone is not task specific. The influence of naloxone on retention was time dependent in both tasks. The results showed that the drug must be present for a considerable period beginning soon after the onset of memory consolidation in order to be effective. For inhibitory avoidance, it was necessary to administer naloxone immediately after training, and because of its short duration of action, again 30 min later. In the active avoidance task, naloxone was effective only when given both immediately before and, as in the inhibitory avoidance task, within 30 min after the eight acquisition trails. These results provide strong evidence that naloxone influences memory and suggest that endogenous opioid systems are involved in memory storage processes.