Antiserum to arginine8-vasopressin was microinjected bilaterally into the dentate gyrus of the dorsal hippocampus and the effect of passive avoidance behavior was studied. After the single learning trial of a passive avoidance response, immediate bilateral injection of 1 microliter antiserum (diluted to 1/50) attenuated passive avoidance responding 24 hr later. In immunocytochemical control studies with injection of undiluted antiserum into the dentate gyrus a spreading was observed towards the ventral hippocampus and the dorsal septum. Additionally, administration into the lateral ventricle of 2 microliters of 1/50 dilution of the antiserum did not affect the behavior. For an attenuation of passive avoidance behavior via intraventricular injection, 2 microliters of a 1/10 dilution of anti-AVP was required. These data suggest that endogenous vasopressin in the septo-hippocampal system might be involved in memory processes.