The association between the class I and class II histocompatibility antigens (HLA) and the severity of alcoholic liver disease was studied in 102 alcoholic patients (64 males and 38 females) with liver disease. According to histologic diagnosis 41 patients had a mild hepatic lesion (12 with minimum changes, 15 with steatosis and 14 with fibrosis) and 61 patients had severe hepatic lesion (13 with alcoholic hepatitis, 35 with cirrhosis and 13 with cirrhosis and alcoholic hepatitis). No differences were found between the two groups in regards to sex, quantity and length of alcohol consumption, although the patients with mild hepatic lesion were younger than those with severe hepatic lesion (41.2 +/- 8.2 and 47.8 +/- 11.6 years, respectively). The prevalence of the A30, B16, B47, Bw56, Cw1, Cw5 and Cw7 antigens was higher in the alcoholics than in the controls, although only the A30 (12.7% vs. 4.4%, p < 0.04) and the Bw56 antigens (3.9% vs 0.1%, p < 0.001) remained significant when the p value was corrected by the number of antigens studied. These differences were due to a greater prevalence of the A30 antigens (17.0% vs. 4.4%, p < 0.001), B16 (24.3% vs. 7.5%, p < 0.01) and Bw56 (7.3% vs 0.1%, p < 0.001) in patients with mild hepatic lesion versus the controls. In contrast, these antigens were present in similar numbers in patients with severe hepatic lesion and in the controls. On the other hand, no differences were observed regarding the prevalence of the class II HLA antigens between the alcoholics and the controls, or between the two alcoholic groups. These data suggest that the alcoholics with A30, B16 and Bw56 antigens are less susceptible to developing severe liver disease.