Since we demonstrated previously that alcohol dehydrogenase (ADH) is distributed predominantly in zone 3 of the hepatic acinus, we have investigated the usefulness of determinations of serum ADH activity in the assessment of hepatic injuries. The measurement of serum ADH activity appears to be useful for the detection of acute and early centrilobular hepatic damage, as deduced from the results obtained from experimental hepatic injuries produced by bromobenzene, hypoxia and acute administration of ethanol. Whereas serum ADH activity increased slightly after the generation of an acute ethanol load in rats which were given ethanol chronically, the hepatic content of ADH tended to decrease. Moreover, a rather selective reduction of hepatic ADH activity was found in zone 3 of the hepatic acinus. Thus, it is conceivable that chronic alcoholic injury to the liver may result in persistent release of ADH from hepatocytes resulting in a relatively low elevation of the level of the enzyme in the blood, rather than a sudden release of the enzyme leading to a sharp increase in the serum enzyme activity.