We conducted an association study between genetic variants of C-type natriuretic peptide gene (CNP) and hypertension in a Japanese population. We found four genetic variants, two in the promoter region, one missense mutation, and one in the 3′-untranslated region (3′-UTR), and genotyped all four variants in 2,006 subjects recruited from the Suita study. One of the variants, G2628A in 3′-UTR, was found to be associated with blood pressure. Multiple logistic analyses indicated that the genotype of the G2628A polymorphism (GG= 1, GA+ AA= 2)(p= 0.0034), sex (p= 0.0288), alcohol consumption (p= 0.0002), age (p< 0.0001), and body mass index (p< 0.0001) were predictors of hypertension. The odds ratio of the GA+ AA genotype over the GG genotype for hypertension was 1.40 (p= 0.0034, 95% confidence interval (CI) 1.12–1.75). Multiple logistic analyses in a younger subpopulation aged below 65 years indicated that the odds ratio of the GA+ AA genotype over the GG genotype for hypertension was 1.58 (p= 0.0024, 95% CI 1.18–2.12). Thus, the CNP G2628A polymorphism made an even greater contribution to hypertension in the younger subpopulation.(Hypertens Res 2002; 25: 727–730)