Patients with chronic hepatitis C infection show a gradual progression of fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied whether the progression of liver fibrosis differed among Japanese subjects who were infected with different hepatitis C virus (HCV) genotypes. In 527 patients we examined whether there was a relationship between gender, age, history of blood transfusion, interval between date of blood transfusion and date of liver biopsy or date of diagnosis of HCC, serum alanine aminotransferase level, platelet count or HCV genotype, with the extent of liver fibrosis, classified into four stages (F1-F4). Moreover, we compared the mean rate of liver fibrosis progression per year in patients with each HCV genotype. Patients who had a higher fibrosis score tended to be older, have a lower platelet count and a longer interval since blood transfusion than those who had a lower fibrosis score. The mean rate of liver fibrosis progression was 0.12 +/- 0.15 stages per year after the blood transfusion. However, the progression rate of liver fibrosis in patients who had received a blood transfusion when they were > or = 30 years of age was 0.19 +/- 0.22, while the progression rate of liver fibrosis in the patients who had received a blood transfusion when they were < 30 years was 0.09 +/- 0.09. In conclusion, chronic hepatitis C is a progressive disease, and patients with genotype 1b, 2a and 2b have a similar rate of progression of liver fibrosis. Particular attention should be paid to patients who are infected with HCV when > or = 30 years of age, because intrahepatic fibrosis rapidly progresses in these patients.