We evaluated the number of clones and the degree of nucleotide diversity in the HVR of the HCV genome in patients with chronic active hepatitis C who were treated with IFN (interferon). We could not obtain the nucleotide sequence per se of the HCV genome but were able to evaluate the degree of diversity in the nucleotide sequence of the HCV genome using FSSA. Nonresponders to IFN therapy showed significant diversity in the nucleotide sequence, even if their number of HCV clones are small. Responders showed little diversity in the nucleotide sequence, which suggests that their viral clones were composed of populations with less variability in the HVR. IFN therapy had more impact on diversity in the nucleotide sequence than on the number of HCV clones.