This study was conducted to clarify if the long-term histological outcome among patients with chronic hepatitis C differs according to whether they are infected with genotype 1 or 2 hepatitis C virus (HCV). We examined 140 patients with chronic hepatitis C. The HCV genotype was determined by the enzyme-linked immunosorbent assay (ELISA) based on genotypes 1 and 2 specific recombinant proteins; genotype 1 was found in 100 patients (96 were 1b and 4 were indeterminate) and genotype 2 in 36. The two groups showed no significant difference for any clinical background features. Deterioration of the grade of liver histology during the follow-up period was seen in 68.0 percent of the patients with genotype 1 as compared with 41.7 percent of those with genotype 2 (P < .01). Similarly, the deterioration of the stage of liver histology was more common in the former group than in the latter (63.0 percent and 38.9 percent respectively; P < .05). The mean serum HCV-RNA titer was significantly higher in the patients with genotype 1 than in those with genotype 2 (P < .001), and multivariate analysis showed the titer was one of the independent factors of the deterioration of the stage (P = .0044). This phenomenon may be related in part to the difference in pathogenicity between the two HCV genotypes. In conclusion, our results suggest that more severe progression of chronic hepatitis C is seen in patients showing genotype 1b compared with those with genotype 2.