Male Swiss mice were tested 48 h after training in a one-trial step-through inhibitory avoidance task. Immediately post-training i.p. injection of the GABA antagonist picrotoxin (0.3–3.0 mg/kg), at nonconvulsive doses, induced a dose-dependent modification of retention performance. The lower doses of picrotoxin (0.1–1.0 mg/kg) enhanced retention, whereas the highest dose (3.0 mg/kg) impaired retention. Picrotoxin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of picrotoxin on retention performance were not due to nonspecific proactive effects on response latencies. The enhancing effects of picrotoxin (1.0 mg/kg) on retention were time-dependent, which suggests that picrotoxin enhanced storage of recently acquired information. The enhancement of retention induced by picrotoxin (1.0 mg/kg) was prevented by the vasopressin receptor antagonist, AAVP (0.01 μg/kg, s.c.) administered immediately after training, but prior to picrotoxin treatment. This dose of AAVP did not affect retention by itself, either under the standard experimental conditions, or in mice trained with a high footshock. Low subeffective doses of picrotoxin (0.1 mg/kg, s.c.) administered immediately after training, and hypertonic saline (1 ml of 0.5 M NaCl, i.p.), given 10 min after training, interacted to improve retention. Considered together, these findings suggest that the better retention performance induced by post-training administration of picrotoxin could result, at least in part, from an endogenous release of vasopressin.