We evaluated the effect of general anesthesia induced by 45 mg/kg iv pentobarbital sodium or by 75 mg/kg iv alpha-chloralose plus 500 mg/kg iv urethan on the response of cerebral arterioles to hypercapnia in rabbits equipped with chronically implanted cranial windows for the observation of the cerebral microcirculation. Both types of anesthetic induced approximately comparable anesthesia and depressed the responsiveness to CO2 to an equal extent. There were no changes in resting vessel diameter or in mean arterial blood pressure induced by either anesthetic, but both anesthetics increased end-expiratory PCO2 during room air breathing. The findings show that anesthetics depress the responsiveness of cerebral arterioles to hypercapnia. A decrease in cerebral metabolism and/or direct effects of the anesthetics on cerebral vessels may be involved.