HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy.