In the behavioral despair test in mice, oxytocin, i.p. injected 60 min before testing, significantly reduced the duration of immobility at doses of 0.250-1.0 mg/Kg; the effect being similar to that of imipramine (7.5-30 mg/Kg i.p.). A more powerful effect was obtained with a 10-day treatment schedule. In the learned helplessness test, oxytocin (0.500 mg/Kg/day i.p. for 8 days) significantly reduced the escape failures and the latency to escape, the effect being even more intense than that of imipramine (20 mg/Kg/day i.p. for 8 days). These results show a new behavioral effect of oxytocin, and further support its role of CNS regulatory peptide.