These experiments examined the effects of a novel experience prior to training or retention testing on 24-h retention of an inhibitory avoidance response in mice. The experiments were based on previous evidence that novel training experiences release hypothalamic β-endorphin. When given 1 h prior to training, the novel experience (clinging to the wire-mesh ceiling and exploring a small box) attenuated the memory-enhancing effects of post-training administration of naloxone as well as the enhancing effects of β-endorphin administered prior to the retention test. The novel experience given prior to training did not block the enhancing effects of post-training administration of epinephrine. β-Endorphin and the novel experience both enhanced retention performance when administered 1 h (as well as 3 but not 6 h) prior to the retention test. The enhancement found with both treatments was blocked by simultaneous administration of naloxone or by administration of propranolol a few minutes prior to the retention test. The findings of these experiments are consistent with the view that the effects of the novel experience are due to a release of endogenous β-endorphin and provide additional evidence that the effects, on retention, of naloxone given post-training and β-endorphin given prior to a retention test, are based on training-induced release of β-endorphin.