Incidence of polymorphisms on exon 4 (CGC vs. CCC, p53Arg vs. p53Pro, A2 allele vs. A1 allele at codon 72, respectively) of the p53 gene was compared in 75 cases with hepatitis C virus (HCV) infection and 232 noninfected control subjects in a defined geographical area in Japan. Polymorphism was analyzed by the polymerase chain reaction-single strand conformation polymorphism method using DNA from peripheral blood leukocytes. When all cases and controls were compared, there was no significant correlation between hepatitis C virus (HCV) infection and the p53 polymorphism in question. However, when male cases infected with HCV type 1b, the most common viral genotype, were compared with controls matched by sex and age, significantly higher homozygotes for p53Pro were found in cases compared with controls (P=0.039). Significantly higher allelic frequency of this polymorphism was also observed with cases (P=0.010). We found no significant statistical difference between the p53 polymorphism and other genotypes of HCV (2a, 2b and others). On the basis of our study we believe there exists a significant correlation between male homozygotes for p53Pro with HCV type 1b infection.