The clinical significance of serum antibodies against alcohol-altered rabbit hepatocytes was evaluated in 91 patients with alcoholic liver disease. Patients were divided into two groups according to the presence or absence of those antibodies at the time of first admission, and their clinical, biochemical, and histological findings were compared. In 38 seropositive patients, the total amount of ethanol consumption as well as serum activity of glutamate-oxaloacetate transaminase, serum levels of total bilirubin, gamma-globulin, IgG, and IgA were all significantly higher than in 53 seronegative patients. In addition, the extent of fibrosis, alcoholic hyalin, cholestasis, and lymphocytic and polymorpholeukocytic infiltrations in the liver were all significantly greater in the seropositive patients. Histological changes were compared in the 16 patients who continued to drink alcohol and who received repeated liver biopsies. Seven out of eight patients who were seropositive at the time of the first liver biopsy showed histological deterioration, whereas one of the eight seronegative patients showed a slight progression. These results suggest that the presence of serum antibodies against alcohol-altered liver cell membrane delineates a group of alcoholic patients with severe, advanced liver disease characterized by a tendency to progress with continued alcohol ingestion.