The rates of ethanol oxidation in various species are linked to the rates of general metabolism, and more specifically that of O2 utilization by the liver. After chronic ethanol administration, increased oxidation of ethanol is accompanied by increased total hepatic O2 utilization, as studied in the whole animal, the perfused liver, and isolated liver slices. The correlation is particularly striking in the spontaneously hypertensive rat. This linkage makes the liver of the chronically ethanol-consuming rat abnormally vulnerable to hypoxic damage. Exposure to 5% oxygen atmosphere for 6 hours produced major elevations of SGOT and SOCT activities and marked centrilobular necrosis, in alcohol-treated animals but not in controls. The same differential susceptibility was found to acute anemia produced by bleeding. The possible relation of these findings to alcoholic liver damage in humans is discussed.