Our previous demonstration of sexual dimorphism in the antidiuretic response to exogenous vasopressin prompted us to investigate the response to moderately high levels of endogenous vasopressin stimulated by water deprivation in conscious rats. After 24 h water deprivation, urine flow was significantly higher and urine osmolality lower in females than in males. Plasma concentrations of vasopressin were higher in females than in males after water deprivation, but plasma osmolality did not differ. Gonadectomy, which had no effect in dehydrated males, decreased urine flow and increased urine osmolality in females to levels observed in intact and gonadectomized males. Spontaneous water intake was also measured and found to be lower in males and estrous females than in females in the other phases of the estrous cycle. These observations support the concept that there is a gender difference in the antidiuretic responsiveness to endogenous vasopressin, that this difference is dependent upon the ovarian hormones, and that it may lead to differences in consumptive behavior.