Arginine vasopressin (AVP) is thought to act as an antipyretic in the ventral-septal area (VSA) of the brain. As AVP content of this area has been shown to be virtually eliminated following long-term castration, we have tested the hypothesis that castrated rats would display enhanced fevers. Four months after castration (or sham castration), male Wistar rats were given prostaglandin E1 (200 ng), purified interleukin 1 (25 U), or saline (5 microliters) into a lateral cerebral ventricle. Castrated rats displayed fevers of longer duration, reflected as significantly enhanced thermal indexes, than did age-matched sham-operated controls. Castrated rats also were less able to defend their body temperatures to ambient heat stress but not to ambient cold. AVP content of VSA and lateral septum, but not of hippocampus, of castrated rats was significantly reduced; oxytocin content of the three areas was unchanged following castration. These data support earlier studies concerning effects of castration on septal AVP content and are consistent with the possibility that AVP is an antipyretic in the VSA of the rat.