The aim of the study was to evaluate the efficacy of combination therapy with interferon-alpha (IFN-alpha) and ribavirin in patients with chronic hepatitis C and normal alanine aminotransferase (ALT) values. In this retrospective study, 12 HCV-RNA positive patients (7 males and 5 females, mean age 38.1 years), treated between 1998 and 2001, with normal or near normal ALT values on three consecutive occasions and histologically mild disease were identified. During the induction period of four weeks they received 56 MU IFN-alpha 2b and ribavirin 1000 mg daily. During the next 44 weeks they received 3 MU IFN-alpha 2b three times a week with ribavirin 1000 mg daily. Seven out of 12 (58%) patients were HCV-RNA negative at the end of the therapy (end-of-treatment-response) and 5 of 12 (42%) showed sustained virologic response at 6 months. No significant elevation of aminotransferase values was recorded during therapy. Patients with mild chronic hepatitis C and normal ALT levels respond well to combination therapy with interferon and ribavirin, similar to those with elevated ALT levels. As long as the natural history and long-term outcome of these patients are not completely known, this might be a beneficial treatment option.