The effectiveness of recombinant interferon-alpha 2b (rIFN-alpha 2b) in eradicating hepatitis C virus (HCV) RNA from serum has not been completely assessed. We studied 39 patients with compensated chronic hepatitis C diagnosed by liver biopsy and positive HCV RNA measured by polymerase chain reaction (PCR). Group I consisted of 26 patients treated with 3 MU of rIFN-alpha 2b for 6 months; group II, 13 control patients observed for six months; and group III, 12 out of 13 patients from group II who subsequently received 5 MU of rIFN-alpha 2b for 6 months. In group I, 11 out of 23 (47.8%) patients who completed treatment had an immediate response and five (21.7%) had a sustained response to therapy six months after treatment. No response was observed in patients from group II. In group III, 7 out of 12 (58.3%) patients who completed treatment had an immediate response and none had a sustained response. Considering all patients who completed rIFN-alpha 2b treatment, HCV RNA remained positive at the end of therapy in three of five sustained responders (60%), six of 13 patients who relapsed (46.1%), and in all nonresponders (100%). HCV RNA was positive 6 months after therapy in four (80%), 13 (100%), and 17 (100%) patients respectively. All patients with a sustained response had normal aminotransferase levels 18 months after therapy. We conclude that in chronic hepatitis C rIFN-alpha 2b causes a significant immediate response but this is not sustained, only 2.8% of treated patients had a sustained loss of HCV RNA. Normal aminotransferase persist in the long term, despite persistence of HCV RNA.