The effects of α-interferon therapy were evaluated in a prospective, randomized, double-blind, controlled trial of recombinant human interferon alfa-2b versus placebo in patients with well-documented chronic non-A, non-B hepatitis (type C). Forty-one patients, of whom 37 (90%) had hepatitis C virus antibodies in their serum, were enrolled in the trial. Twentyone patients received interferon (2 million units) and 20 received placebo as subcutaneous injections three times weekly for 6 months. Mean serum aminotransferase activities and liver histology improved significantly in interferon-treated patients but not in placebo recipients. Ten interferon-treated patients (48%) had a complete response to therapy as shown by a reduction of mean serum aminotransferase activities into the normal range during therapy; three more patients had a partial response with aminotransferase activities decreasing by more than 50% on average. In follow up, however, serum aminotransferase levels usually returned to pre-treatment levels; at 6 to 12 months after stopping interferon, only two (10%) patients still had normal aminotransferase activity. These results indicate that α-interferon therapy is beneficial in reducing the disease activity in chronic hepatitis C. Only a minority of patients, however, appear to have a long-term response. In this study, interferon was generally well tolerated, with only one patient discontinuing therapy because of adverse effects.