To determine whether genetically determined immune response factors could be involved in the pathogenesis of hepatocellular carcinoma, we performed HLA-A and HLA-B typing in 55 black patients with histologically-proven hepatocellular carcinoma, and HLA-DR and HLA-DQ typing in 47 of these patients. The HLA typing was also carried out in a control group of normal black patients. The HLA typing was done by a standard microlymphocytotoxicity method. No difference in HLA-A, HLA-DR and HLA-DQ frequencies between patients and controls were noted. HLA-B21 was present in 10.9% of patients compared to 1.8% of control subjects (corrected p < 0.005; relative risk = 6.6) and HLA-B49 was present in 7.3% of patients compared with 1.1% of normal control subjects (corrected p < 0.007; relative risk = 7.1). These findings suggest that genetic factors may play a role in the pathogenesis of hepatocellular carcinoma.