Seven patients with chronic hepatitis C, six hemophiliacs and a patient with von Willebrand's disease, were treated with interferon-alpha (IFN-alpha). Either 9 MU of recombinant IFN-alpha 2a or 3 MU of lymphoblastoid alpha-IFN was administered daily for 2 weeks and then three times a week for 22 weeks. Liver histology, hepatitis C virus (HCV) genotypes, and HCV-RNA levels in sera were investigated in all of the patients before IFN therapy was instituted. Liver histology was classified by the European classification. HCV genotyping conformed to the so-called Okamoto's classification. HCV-RNA levels in sera were quantitated by competitive polymerase chain reaction, using mutant RNA. Liver histology, HCV genotype, and serum HCV-RNA level (copies/ml) in each patient were: patient 1, chronic persistent hepatitis, type II, 3 x 10(3) respectively; patient 2, chronic active hepatitis (CAH) 2a, type III, 6 x 10(4); patient 3, CAH2a, type IV, 2 x 10(5); patient 4, CAH2b, type I, 2 x 10(7); patient 5, CAH2b, type II, 8 x 10(4); patient 6, CAH2b, type III, 7 x 10(6); and patient 7, CAH2b, type IV, 1 x 10(7). Sustained elimination of HCV was achieved in patient 3 and temporary elimination was achieved in patients 1 and 2. The other patients showed persistent HCV-RNA positivity in sera both during and after IFN treatment. Poor responsiveness to IFN was observed in patients with relatively progressive liver histology and high levels of HCV viremia.