Our data demonstrate that (a) marked modifications in ADH activity, as found in patients with atypical ADH or in subjects with alcoholic liver disease, are not accompanied by parallel alterations in the kinetics of ethanol disappearance, suggesting that ADH activity per se does not limit ethanol metabolism in viva, (b) hepatic high-Km ALDH activity is decreased in patients with liver disease independent of alcoholism, and therefore decreased ALDH activity cannot be considered as a primary defect in alcoholism but as a consequence of liver damage. and (c) erythrocyte ALOH does not reflect hepatic high-Km ALOH.