SUMMARYChronic ethanol consumption, in a diet which leads to a fatty liver, results in an increase in the rate of ethanol oxidation in isolated rat hepatocytes. The percent increase (30%‐40%) is similar to that previously found in vivo, in the same model system.1,11This increase does not correlate with the activity of alcohol dehydrogenase, which was slightly decreased after chronic ethanol consumption.1,16The increase in ethanol oxidation is not associated with a hypermetabolic state of the liver since oxygen consumption with a variety of substrates was not enhanced after chronic ethanol consumption. Approximately 40%‐50% of this increase persists in the presence of an inhibitor of alcohol dehydrogenase, inhibitors of mitochondrial oxygen consumption and inhibitors of the malate‐aspartate shuttle. The increase persists in the presence of ouabain, dinitrophenol and various shuttle metabolites (in the presence and absence of dinitrophenol). Chronic consumption of ethanol results in hypertrophy of the smooth endoplasmic reticulum and an adaptive increase in the ability of microsomal preparations to oxidize ethanol to acetaldehyde.1,11The fact that part of the increase in ethanol oxidation which occurs after chronic ethanol administration persists in the presence of the various additives discussed above, indicates that pathways that are independent of alcohol dehydrogenase contribute to this metabolic adaptation. These data extend the observation that the metabolic adaptation found after chronic ethanol consumption was not abolished by 2mM pyrazol