Hepatitis C virus (HCV) cDNA sequence in the nonstructural region NS3 was amplified from the serum of 66% French non-A, non-B hepatitis patients by the nested polymerase chain reaction. A 407 base-pair sequence was determined from four such cases, which revealed the presence of two different virus genotypes F1 (three cases) and F2 (one case) with 19-20% sequence divergence. F1 showed close homology (97.5%) to the prototype US isolate, but only limited (79%) homology to the reported Japanese isolates. In contrast, F2 had 91.6% homology to the Japanese isolate, but only 81% homology to the prototype US virus. Hybridization of the amplified products from 50 French samples with labeled F1 and F2 fragments suggested the F1-related strain(s) as the major hepatitis C virus genotype. Further studies involving a greater variety of samples will confirm whether the F1-related strain is the predominant hepatitis C virus strain circulating in France. Such data will have important implications for the PCR detection of HCV infection and production of HCV vaccines.