To contribute to the study of the genetic variability of hepatitis C virus (HCV) we have determined the nucleotide sequence of the E2/NS1 and NS3/NS4 regions of a French isolate using the polymerase chain reaction. Comparison of these nucleotide sequences with those available for American and Japanese isolates showed a significant genetic variability: 5 to 33% and 2 to 30% at the nucleic acid and amino acid levels, respectively. The genetic variability is higher in the E2/NS1 (13 to 33% and 12 to 30% at the nucleic acid and amino acid levels, respectively) than in the NS3/NS4 (5 to 21% and 2 to 7%) regions. The sequence of the French isolate is more closely related to that of the American HCV prototype than to the Japanese HCV isolates. This study confirms the extent of HCV genetic variability.