Forty-eight unrelated North Indian patients with non-cirrhotic portal fibrosis were studied for the distribution of HLA-A, B and DR antigens. No significant differences were observed in the distribution of HLA-A and B locus antigens. In the DR locus, the frequency of DR3 was significantly increased in the patients as compared to the controls (71.7% vs 26.1%, X2 = 25.3), while HLA-DR2 was significantly reduced (X2 = 11.3). Another striking observation was the presence of DR7 in all males negative for HLA-DR3. The results suggest an autoimmune pathogenesis of the disease and that susceptibility to non-cirrhotic portal fibrosis may be HLA class II mediated, with HLA-DR3 influencing susceptibility and DR2 conferring protection. Other genetic factors are also involved.