The effects of inspiration of low O2 and/or high CO2 gas mixtures on relative tissue PO2 and perfusion of brain and muscle were studied in 60 pentobarbital-anesthetized spontaneously respiring rats. These animals were studied in intact condition, after administration of phenoxybenzamine hydrochloride, 2 mg/kg, or after bilateral denervation of their carotid bodies. In the intact rats, the relative tissue PO2 ratio of biceps brachii to cerebral white matter always decreased after exposure to the above gas mixtures. This indicated a better maintenance of O2 supply to demand in the brain than in muscle. After either carotid denervation or alpha adrenergic blockade, this change in the ratio was no longer significant. Further, cerebral blood flow responses to these gas mixtures were attenuated (avg + 5.3%) compared to previous work in intact rats. It is concluded that the brain is best protected against hypoxia and/or hypercapnia when the carotid chemoreflex is intact.