Treatment with alfa-interferon alone yielded poor results in children with chronic hepatitis C and was not generally recommended. Owing to limited experience with combination therapy in children, the aim of the study was to evaluate the efficacy and tolerability of alfa-interferon 2b in combination with ribavirin in these patients with different routes of viral transmission. In an uncontrolled pilot study, 41 children and adolescents ranging from 3 to 16 years were treated with alfa-interferon at a dose of 3 or 5 MU/m 2 3 times weekly in combination with oral ribavirin (15 mg/kg/d) for 12 months. The mode of infection was unknown in 4, parenterally transmitted in 16, and vertically transmitted in 21 children. Forty patients completed the study. Eleven children, who remained hepatitis C virus (HCV)-RNA positive 6 months after the beginning, discontinued therapy. One boy stopped treatment because of side effects. At the end of treatment 25 patients were HCV-RNA negative (61%). All individuals remained HCV-RNA negative during the 6-month follow-up period. Nine of 15 children with parenteral (56.3%), 14 of 21 with vertical (66.6%), and 2 of 4 with unknown route of infection responded. Side effects included minor clinical signs such as fever, flu-like symptoms, anorexia, and more severe signs (21.4%) such as the development of thyroid autoantibodies and impairment of thyroid function. In conclusion, combination of alfa-interferon with ribavirin seems to be an important advance in the treatment of chronic hepatitis C in children and adolescents. This also is true for both vertically infected patients and for individuals with normal transaminase levels before therapy. (H EPATOLOGY 2002;36:1280-1284.)