Vasopressin and oxytocin cause behavioral excitation after intracerebroventricular injection in mice. This effect is short-lasting, suggesting that the peptides are rapidly inactivated in the brain. Co-injection of microgram amounts of amastatin, an aminopeptidase inhibitor, prolonged the effect of both vasopressin and oxytocin. Amastatin did not induce large vasopressin-like behavioral effects by itself, nor did it significantly potentiate the action of 1-deamino[1,6-dicarba, 8-arginine] vasopressin (Asu-AVP), an analog that lacks the N-terminal amino group. The effect of Asu-AVP, but not that of vasopressin, was potentiated by phosphoramidon, an inhibitor of neutral metalloendopeptidase ("enkephalinase A"). These results support previous suggestions that vasopressin and oxytocin are inactivated mainly by aminopeptidase action following intracerebroventricular injection.