Hepatitis C virus (HCV) virions have been shown to be bound to antibodies in patients with chronic HCV infection. The sera from patients infected with genotype 1b HCV contained more antibody-free virions than those from patients with genotype 2a/2b HCV. When compared at the same levels of serum HCV RNA, free virion titers of genotype 2a/2b-infected patients were much lower than those of genotype 1b-infected patients, indicating that a larger fraction of HCV virions are bound to antibodies in the former than in the latter. The gene segments encoding the hypervariable region (HVR) 1, a principal neutralization epitope, of HCV were amplified from the patients' sera by reverse transcription-polymerase chain reaction. The majority of genotype 2a/2b-infected patients had very similar HVR 1 sequences to one another, whereas patients infected with genotype 1b HCV had highly heterogeneous sequences. Differences in the amount of antibody-free virion and HVR1 sequence variability between genotypes may have an implication in HCV pathogenesis.