Inhaled anesthetics may have an effect on the microcirculation through selective alteration of receptor-mediated control. Halothane was chosen because its actions in the microcirculation have been determined previously. Serotonin has received recent attention as a potential mediator of vascular changes in a number of disease states. We obtained concentration-response curves for serotonin-induced constriction of large arterioles and dilation of small arterioles (less than 60 microns diameter) in the cremaster muscle of halothane-anesthetized and decerebrate rats. Cremaster muscles were prepared for microscopic viewing, leaving the neural and vascular supply intact. Serotonin concentration-response curves were obtained before and after receptor antagonist application. Large arteriole constriction was not affected by halothane. Dilation of small arterioles was decreased in halothane-anesthetized animals but enhanced in the presence of methysergide, a nonspecific antagonist. These data indicate that halothane interferes with occupancy of 5-hydroxytryptamine receptors.