We examined 14 patients with hepatitis C caused by infection with the hepatitis C virus-II genotype to understand differences in responsiveness to interferon. The patients were classified into two groups according to their response to interferon: eight responding and six non-responding patients. The 5' noncoding and structural regions of the hepatitis C virus-II genome from each patient specimen were amplified by reverse transcription followed by the polymerase chain reaction. The nucleotide sequences of these amplified DNAs were then determined. By comparing the nucleotide sequences and the deduced amino acid sequences of samples from both groups, no group-specific sequence was observed in the analyzed regions despite the presence of considerable sequence diversity. However, additional cysteine residues were observed in half the responding group. The degree of micro-heterogeneity in hypervariable region 1 of the hepatitis C virus in relation to the sensitivity to interferon treatment was also examined; however, no significant correlation was observed. In addition, frequent alterations in the amino acid sequences were observed in hypervariable region 1 during the course of interferon treatment.