The effects of serotonin (5-HT) on the microvasculature of cremaster muscles were compared in decerebrate, ketamine- and pentobarbital-anesthetized rats. 5-HT-induced constriction of large distributing arterioles was enhanced in the ketamine- and pentobarbital-anesthetized rats. Precapillary arterioles of pentobarbital-anesthetized animals were more sensitive to 5-HT-induced dilation than either decerebrate or ketamine-anesthetized animals. The response of vessels to two 5-HT receptor antagonists (methysergide and LY53857) were unchanged by the anesthetics. Our findings suggest that both ketamine and pentobarbital enhance the microvascular response to 5-HT, but that these changes are not due to an alteration of receptor sensitivity.