To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to clarify the relationship between genotype and the pathogenesis of HCV infection, 1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center in Taiwan were studied during 1995–1997. HCV genotypes and viral loads were determined using Okamoto's method and branched DNA assay, respectively. Genotype 1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral center (47.0%). By contrast, genotype 2a was the major HCV type in Masago (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively correlated to age, regardless of study populations (P < 0.01). Based on multivariate analysis, the significant factors associated with the presence of cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C patients were genotype 1b and age. In conclusion, these results underline that independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan, concomitant with a changing relative prevalence of HCV genotypes in relation to age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic properties of HCV genotypes are probably responsible for the association between genotype and the pathogenesis of HCV infection. J. Med. Virol. 65:58–65, 2001. © 2001 Wiley-Liss, Inc.