1. The effect of pentothal anesthesia was examined in 9 subjects on whom 19 observations were made. Blood was drawn simultaneously from the right and left internal jugular veins and the femoral artery in order to determine the right and left cerebral arteriovenous oxygen differences and the right and left cerebral blood flows, which were measured according to the method of Kety and Schmidt to calculate cerebral metabolic rate. When results from both right and left sides are averaged, the oxygen consumption of the brain in the unanesthetized man is 3.3 cc. oxygen/100 gm. of tissue/minute. This value, however, represents two groups: a higher one with 3.9 cc. oxygen/100 gm. of tissue/minute and a lower with 2.7. Because of the asymmetric venous return, the cortical component usually appears preponderantly in one of the two internal jugular veins and it is concluded that the portion of the brain with the higher metabolic rate is the cortex.2. In every instance, pentothal anesthesia induced a depression in metabolic rate. The average during the second and third stages of anesthesia is 2.1 cc. oxygen/100 gm. of tissue/minute, a reduction of 36% from the control value. The pattern of pentothal anesthesia shows that cortical oxidations are depressed earlier and more profoundly than those of the rest of the brain, which in turn may also be subjected to metabolic inhibition.3. Because of some effects of pentothal, which cannot be attributed to metabolic inhibition, it is concluded that pentothal narcosis is on a bipartite basis, including metabolic depression as one factor and inhibition of nerve function as another. The clinical signs of pentothal narcosis can be best explained on this bipartite basis.4. In the resting individual, the high metabolism of the cortex is correlated with its rapid blood flow. It is probable that the parts of the brain with the higher metabolic rates possess a greater vascular complement and that this is a structural adaptation to metabolic requirements. On the other hand, the retarded cerebral blood flow observed with pentothal anesthesia is functional and in part is a response to a decreased metabolic rate. The depression of metabolism induced by pentothal alters both the cerebral arteriovenous oxygen difference and cerebral blood flow. In most instances, both are decreased and, therefore, each of these factors is modified to account for the fall in cerebral metabolic rate.