The influence of hepatitis C virus (HCV)-genotypes on the responsiveness to interferon- (IFN-alpha) was studied in 116 patients with proven chronic hepatitis C. 88 of 116 (76%) patients were infected with HCV-genotype 1, 7 (6%) with HCV-genotype 2, and 21 patients (18%) with HCV-genotype 3. All patients received at least 3 MU recombinant IFN-alpha-2a, 2b or lymphoblastoid IFN-alpha tiw for at least 6 month (total IFN-alpha dose per patient 216-720 MU, mean 360; treatment duration 6-12 month, mean 8). The follow-up after cessation of therapy was 9-48 months (mean 25). Sustained normalization of the aminotransferase levels was observed in 20 (17%) of the 116 patients. 10 of the 88 (11%) patients with HCV-genotype 1, 7 of the 21 (33%) patients with HCV-genotype 3 (p < 0.02), and 3 out of the 7 patients with HCV-genotype-2- infection achieved a sustained remission. No response was observed in 58 (66%) and 3 (14%) patients with HCV-genotype 1 and 3 infections, respectively (p < 0.002). All but one of the sustained responders remained HCV-RNA negative during the entire follow-up. There were no significant differences between the sustained responders and the group of non-responders and responders with relapse in relation to age, pretreatment aminotransferase levels, histological activity index, or given IFN-alpha dosage. HCV-genotyping is helpful in evaluating the responsiveness to IFN-alpha and will be of importance considering the indication of therapy.