The efficacy of recombinant interferon-alfa therapy in children with chronic hepatitis C has been evaluated in a randomized, controlled pilot study including 27 patients, aged 2 to 14 years, without underlying systemic diseases. On entry, all patients had abnormal alanine transaminase (ALT) levels, 22 were hepatitis C virus (HCV) RNA positive, 19 had mild chronic active hepatitis, and 8 had chronic persistent hepatitis on liver biopsy. Fourteen children received 5 MU/m2 of recombinant interferon-alfa2b thrice weekly for 4 months. If at this time ALT had been reduced to at least 50% the baseline level, treatment was continued up to 12 months. The other 13 children remained untreated. The whole follow-up period lasted 24 months. Interferon was stopped at 4 months in 4 children because of an ALT increase (2 cases), unchanged ALT and febrile convulsions (1 case), and slight ALT decrease (1 case). This latter patient, however, had normal ALT at 6 months and throughout further follow-up, and cleared HCV RNA, thus behaving as a sustained responder. All 10 children treated for 12 months had normal levels of ALT, and 9 were HCV RNA negative at the end of treatment. Of the 9 children who could be followed to 24 months, 4 relapsed soon after therapy withdrawal and 5 maintained a sustained biochemical and virologic response. Overall, 6 (43%) of 14 treated children had a sustained ALT normalization associated with HCV RNA clearance as compared with only 1 (7.5%) untreated child who had a sustained ALT normalization but did not clear HCV RNA. These results suggest that recombinant interferon therapy, at the regimen used in this study, may induce sustained ALT normalization and HCV clearance in a significant proportion of children with chronic hepatitis C. (Hepatology 1995;22:1623-1627).