As part of a multicenter randomized study 40 patients with chronic hepatitis C (HCV)-infection, 28 kryptogenic and 12 posttransfusional, were treated with recombinant interferon alfa (IFN alpha-2a) for 1 year in a dosage of 3 x 3 Mio. units per week versus dosis escalation after 8 and 16 weeks in serological non-responders. 36 of the 40 patients were followed over 3 years. The rate of patients with normalization of aminotransferases was 42% after two months of therapy, 28% at the end of treatment, 28% after 1 year and 23% after 3 years of follow-up. The polymerase chain reaction (PCR) for detection of HCV-RNA became negative after two months of treatment in 73%, at the end of therapy in 63%, after 1 year follow-up in 63% and after 3 years in 35%. All patients with persisting remission maintained HCV-RNA negative. Dosis escalation was realized in 8 patients without increase of responder rate. Antibodies against IFN alpha-2a developed in 4 (10%) patients without remarkable influence on the IFN-effect. Histological improvement at the end of treatment was observed in 61% including all patients with serological remission. The data support the prognostic relevance of the course of aminotransferases. If aminotransferases are not normalized during the first two months the treatment can be terminated. Persisting normalization of aminotransferases during 1 year after therapy and negative HCV-PCR result indicate maintaining remission.