The activity and the histochemical localization of gamma-GTP in the liver of chronic alcoholics were investigated. Mean serum gamma-GTP activity in alcoholics was 542.5 +/- 337.9 milliunits/ml, and that of patients with nonalcoholic liver disease was 34.3 +/- 22.6 milliunits/ml. Hepatic gamma-GTP activity in alcoholics was significantly increased compared to that in control patients (15.62 +/- 9.29 versus 4.04 +/- 2.67 units/g of liver; p less than 0.001). A significant correlation was observed between hepatic and serum gamma-GTP activity. Light microscopically, a marked gamma-GTP activity was found in the bile canaliculi and a diffuse activity in the cytoplasm in alcoholic livers. By contrast, in the livers of nonalcoholic patients, only slight activity was observed in the bile canaliculi. The electron micrographs showed the enzyme was localized in the microvilli of both the bile canalicular and plasma membranes and the endoplasmic reticulum near the mitochondria in alcoholics. But a very low activity was demonstrated in the plasma membranes in the livers of nonalcoholic patients.