To evaluate the effect of prolonged interferon-α treatment on serum aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with chronic hepatitis C virus infection were treated with 3 MU interferon-α2b thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT levels for at least 1 yr, antibodies to HCV by second-generation tests and liver histological findings consistent with chronic hepatitis C. Before treatment hepatitis C virus RNA was found in serum in 39 of 40 (97.5) patients. Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60) patients, of whom 15 of 24 (62.5) had sustained ALT responses up to 24 wk after treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared from serum in 17 of 40 (42.5) patients, including all sustained responders, one nonsustained responder and one nonresponder. We conclude that 60 wk of treatment with interferon-α2b seems to induce a high percentage of sustained response, which coincides with cessation of viral replication. (Hepatology 1994; 19:280–285).