Some HLA class II alleles and haplotypes were examined by restriction fragment length polymorphism of corresponding DNA fragments amplified by the polymerase chain reaction in 117 patients with chronic hepatitis C in Japan. The prevalence rates were compared between patients and 1216 controls and in 67 patients with liver cirrhosis, of whom 20 had hepatocellular carcinoma and 50 patients with chronic hepatitis who did not have cirrhosis or hepatocellular carcinoma. Notably, DRB1*0405 (49% [95% confidence range 38-60%] vs. 26% [16-40%]; P < 0.05, relative risk [rr] = 2.8) and DQB1*0401 (43% [33-54%] vs. 22% [13-34%]; P < 0.05, rr = 2.1) were detected more frequently in patients with cirrhosis than in those without cirrhosis. By contrast, DRB1*0901 (11% [6-19%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) and DQB1*0303 (11% [6-19%] vs. 36% [25-49%]; P < 0.01; rr = 0.2) were detected less frequently in patients with cirrhosis than those without cirrhosis. Accordingly, the DRB1*0405-DQB1*0401 haplotype was more common (43% [33-54%] vs. 22% [13-34%]; P < 0.05; rr = 2.7), while the DRB1*0901-DQB1*0303 haplotype was less common (9% [4-17%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) in patients with cirrhosis than in those without cirrhosis. These results suggest that there would be HLA class II alleles and haplotypes which may be associated with an accelerated or slower progression of chronic hepatitis C towards cirrhosis and eventually to hepatocellular carcinoma.