Gonadal hormones have been shown to modulate adaptive responses of the mesostriatal dopaminergic system to antipsychotic challenge. We examined the role of endogenous gonadal steroids in the regulation of D1 receptor function after chronic treatment with sulpiride, a D2 specific antagonist. Chronic sulpiride treatment induced a desensitization of striatal D1 receptor-simulated adenylate cyclase activity in intact male rats with no change in the number of D1 or D2 receptors. This desensitization of D1-stimulated adenylate cyclase activity was expressed as a decrease in Vmax with no change in the activation constant. Castration of male rats blocked the chronic sulpiride-induced desensitization of D1 receptor function. Castration of male rats also resulted in a decrease in the number of D1 receptors as measured by [3H]SCH23390 binding. Ovariectomy of female rats had no effect on striatal D1 receptor-stimulated adenylate cyclase activity. Preliminary studies showed no effect of chronic sulpiride treatment on D1 receptor function in intact or ovariectomized female rats. We conclude that testicular hormones have a permissive effect on the expression of the chronic sulpiride-induced desensitization of D1 receptor function.