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Background/aims: The amino acid sequence of NS5A2209-2248, named the "interferon sensitivity-determining region" (ISDR), has been reported to correlate with responsiveness of interferon (IFN) therapy to patients with the hepatitis C virus (HCV) genotype-1b, by several Japanese authors. However, European authors have failed to find this phenomenon, suggesting a difference in HCV-1b isolates between Japan and Europe., Methods: We compared the HCV-1b nucleotide sequences of our Japanese patients and those of other countries quoted from GenBank, using the envelope 1 sequence., Results: A phylogenetic tree analysis revealed two characteristic groups from a geographical viewpoint: one group (NJ group) consists of almost entirely non-Japanese isolates, and the other (J group) of almost entirely Japanese isolates. The isolates other than the NJ and J groups are characterized by their specific nucleotide residue, constructing an individual group (W group). Japanese HCV-1b isolates consist of the J group and W group (approximately 40% and 60%, respectively). Comparative study between the two groups in Japanese patients treated with IFN revealed a strong correlation between ISDR type and IFN responsiveness only in the J group, but not in the W group., Conclusions: These observations convinced us that the existence of the Japan-specific J group is one reason why the ISDR system is useful only in Japan.