The complexity of hypervariable region 1 (HVR1) quasispecies of hepatitis C virus (HCV) in serum and peripheral blood mononuclear cells (PBMCs) was assessed at several time points in 11 patients with chronic hepatitis C. Polymerase chain reaction and single-strand conformation polymorphism analysis revealed that four patients (36%) showed serial changes in the complexity of HVR1 quasispecies, which were identical in both serum and PBMCs; two patients (18%) showed both serial changes in quasispecies and differences in quasispecies between serum and PBMCs; and five patients (45%) showed neither serial changes in nor quasispecies differences between serum and PBMCs. These results demonstrate both the existence of different quasispecies between serum and PBMCs and the infection of PBMCs by HCV.