Thirty-three patients with chronic hepatitis C/non-A, non-B were included in a randomized controlled study of interferon-alpha 2b (IFN-alpha 2b) treatment, 3 x 10(6) U three times weekly for 36 weeks. Using an immunoperoxidase technique, frozen liver biopsy specimens were examined with MoAbs for the presence of T helper cells (CD4), T suppressor/cytotoxic cells (CD8), total T cells (CD2) and B cells (CD22) before and after treatment. beta 2-microglobulin (beta 2-MG) expression on hepatocytes was semiquantified using a scoring system on sections from paraffin-embedded biopsy specimens. Serum levels of beta 2-MG were analysed with a radioimmunoassay technique. Intralobular T helper and T suppressor/cytotoxic cells declined significantly in the treated patients but not in the controls. The portal CD4/CD8 ratio did not change. Before treatment, serum beta 2-MG levels and hepatocyte beta 2-MG expression were significantly higher in patients with chronic active hepatitis compared to patients with chronic persistent hepatitis. Serum beta 2-MG levels increased significantly in responders during IFN treatment, with a maximum after 12 weeks. However, in the liver, the hepatocyte beta 2-MG expression was significantly decreased after treatment. Thus, IFN-alpha treatment does not seem to induce an increased HLA class I antigen hepatocyte expression in chronic non-A, non-B hepatitis, which favours the hypothesis that its anti-viral effects are more important in modulating the disease activity.