We have treated 17 patients with non-A, non-B chronic hepatitis by recombinant interferon alpha (0.3-9 megaunits for 4-28 weeks). In six patients, serum aminotransferase levels fell to normal or near-normal range during treatment. The mean levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 17 patients fell from 156 +/- 80 (mean +/- SD) and 213 +/- 135 at the beginning of treatment to 94 +/- 49 and 112 +/- 71, respectively, at the end of treatment. In 12 patients, liver biopsies were performed before and after (or during) the treatment, and histological activity indices (HAI) were blindly examined by two independent observers. For comparison, we examined histological changes of pre- and posttreatment liver biopsies of 19 patients who were treated by recombinant interferon for chronic hepatitis B. Mean HAI scores improved from 10.0 to 5.4 after treatment in non-A, non-B chronic hepatitis. The most marked reduction was noted in scores of portal inflammation and hepatocellular degeneration and/or necrosis. No such reduction was observed in B-viral chronic hepatitis. These data indicated that rapid biochemical resolution by the treatment was related to histological improvement of the liver in our patients with non-A, non-B hepatitis.