Vasopressin has been reported to be an endogenous antipyretic peptide. The present study assessed whether this peptide has similar effects on stress-induced hyperthermia. Infusion of 3 ng of vasopressin into the lateral ventricle prior to a 40-min restraint stress reduced significantly the hyperthermic response of rats to this stress, compared to saline-injected controls. Half of the vasopressin-injected animals showed an immediate hypothermic response, with a significant reduction in body temperature of 0.34 degree C or more within 10 min; however, the effect of vasopressin on stress-induced hyperthermia remained significant after exclusion of these animals from the analysis. Administration of a V1 receptor antagonist prior to the stress did not affect the hyperthermic response, which may suggest that the hyperthermic response had reached maximal (ceiling) levels. Administration of vasopressin, or of the V1 receptor antagonist immediately after the stress, did not affect defervescence, suggesting that vasopressinergic systems are not implicated in the defervescence process. Thus, the results show that ICV administration of vasopressin reduces stress-induced hyperthermia. The mechanisms underlying the effects remain to be elucidated.