To assess the efficacy of interferon-α in acute hepatitis C, 28 patients with acute posttransfusion hepatitis were randomized to receive 3 million units of recombinant interferon-α three times weekly for 12 wk or no treatment. Biochemical, histological and serological parameters were monitored during 1 yr of follow-up. Serum ALT levels were normal at the end of therapy in 73% of treated patients and only in 38% of control patients (p = 0.06); these differences disappeared at 6 and 12 mo of follow-up. Anti–hepatitis C virus seroconversion occurred later and at a lower rate in the group of patients who received interferon-α. Treated patients had a trend toward less severe hepatic lesions with lower histological activity as compared with the control group, but no statistical differences were observed. No severe side effects of interferon-α were detected during the study. In summary, a 3-mo course of interferon-α in acute hepatitis C is safe and might have some effect in diminishing disease activity only during the treatment period; however, and probably because of a small sample size, no benefit of interferon-α in the long-term outcome of this disease was demonstrated. (HEPATOLOGY 1992;15:767–769).