The role of lipid peroxidation in the pathogenesis of alcoholic liver disease has been a subject of controversy. In order to study this question we measured hepatic glutathione and diene conjugates in liver biopsies from 16 alcoholics with different stages of liver injury and 8 nonalcoholics with liver disease. Patients with alcoholic liver disease were found to have decreased hepatic glutathione compared to patients with liver disease unrelated to alcohol (22.1 +/- 2.5 vs 33.5 +/- 4.6 nmol/mg protein, P less than 0.05). The decrease in glutathione was accompanied by an increase in diene conjugates in hepatic lipids (3.37 +/- 0.14 vs 2.26 +/- 0.21 OD at 232 nm/mg lipid, P less than 0.001). The changes were present in all stages of alcoholic liver damage including fatty liver but unrelated to nutritional status in these patients. They support the concept that lipid peroxidation may be an important mechanism in the pathogenesis of alcoholic liver disease.