Patients with well-documented chronic non-A, non-B (NANB) hepatitis are being evaluated to determine the long-term natural history of this common form of chronic liver disease. A cohort of such patients are available to evaluate experimental therapies for this disease. In a pilot study, 10 patients were treated with alpha- interferon. Follow up shows that 6 seem to have had a long-term apparently complete remission of the hepatitis. In 2 cases the response was favorable but temporary and 2 patients did not respond at all. A prospective, randomized, placebo-controlled, double- blind trial of a six month course of human alpha interferon in patients with chronic NANB hepatitis is underway. Forty one patients have been entered and 26 have completed 6 months of treatment so far. 12 of 13 patients treated with interferon showed some decrease in serum ALT activity and in 7 of these, ALT returned to normal levels after treatment. Mean serum ALT activity did not become normal in any placebo-treated patients. Interferon was generally well tolerated and similar untoward developments were noted in interferon and placebo treated groups.