Recombinant human alpha-interferon was administered to 15 patients with chronic non-A, non-B hepatitis as a part of a pilot study. Patients received injections of 2 million units per day of interferon three times weekly for 16 wk. The treatment schedule was completed in all but one, whose serum aminotransferase levels were continuously elevated during treatment. In seven of the 15 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. However, once the therapy was stopped, a prompt return of aminotransferase levels to pretreatment values usually was observed. After 3 months of follow-up, aminotransferase activities remained normal in only two patients in whom liver histology showed marked improvement in intralobular degeneration and focal necrosis of hepatocytes. Anti-interferon antibody was detected in four patients at the end of therapy, and decreased 2',5'-oligoadenylate synthetase activity occurred in two patients and in another with relapsed aminotransferase level. Whether alpha-interferon therapy could control the disease activity in patients with chronic non-A, non-B hepatitis deserves further evaluation in a prospective controlled trial.