The genes encoding 慣-adducin (ADD1, G460W polymorphism) and angiotensin I-converting enzyme (ACE, T2547C and I/D polymorphisms) have been implicated in essential hypertension (EH) and may influence the blood pressure (BP) regulation through sodium homeostasis. In order to investigate whether the polymorphisms in two genes are associated with EH, we carried out a case-control study of 449 hypertensive cases and age-/gender-matched 459 normotensive controls recruited in the Korean population. The genotypes for these polymorphisms were determined by polymerase chain reaction (PCR) and DNA sequencing technique. The genotype frequency of ACE T2547C polymorphism was significantly different between hypertensive and normotensive subjects, which was only present in females (p=0.02). ACE 2547C homozygosity, in comparison with the other ACE genotypes, was strongly associated with increase in the incidence of hypertension (OR, 1.79; 95% CI, 1.14-2.81, p=0.01) in single-gene analyses. In haplotype and multiple-gene analyses, the group with ACE C-D haplotype had the lowest incidence of hypertension in the presence of the ADD1 460W homozygosity in males (OR, 0.53; 95% CI, 0.33-0.86, p=0.01). The result of pairwise linkage disequilibrium (LD) test between ACE T2547C and I/D polymorphisms was found to be in significant LD (D'=0.96) in our study population. In conclusion, ADD1 and ACE polymorphisms interact to influence positively to increase the risk for high BP in Koreans, suggesting that these genes might predispose to EH.