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. A prospective, randomized, placebo-controlled, double-blind trial of a six month course of human alpha interferon in patients with chronic NANB hepatitis has been completed. Forty-one patients have completed the first 6 month (blinded) phase of the study. Twenty one received interferon and 20 placebo. Mean serum aminotransferase activities and liver histology improved significantly in interferon-treated patients but not in placebo recipients. Eighteen patients who initially received placebo were crossed over to receive interferon for 12 months. They have had a similar response to the patients treated for 6 months, although their long-term response rate may be higher.