The genes encoding α-adducin (ADD1, G460W polymorphism) and angiotensin I-converting enzyme (ACE, T2547C and I/D polymorphisms) have been implicated in essential hypertension (EH) and may regulate the blood pressure (BP) regulation through sodium homeostasis. In order to investigate whether the polymorphisms in these genes are associated with EH in Koreans, we carried out a case-control study of 449 hypertensive cases and age-/gender-matched 459 normotensive controls recruited from Cardiovascular Genome Center of Yonsei University in Korea. The genotypes for these polymorphisms were determined by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and the allelic-specific PCR for I/D, T2547C, and G460W, respectively. The genotype frequency of ACE T2547C polymorphism was significantly different between the hypertensive and the normotensive subjects, which was only present in females (P = 0.019). ACE 2547C homozygosity, in comparison with the other ACE genotypes, was strongly associated with increase in the incidence of hypertension (OR, 1.788; 95% CI, 1.139-2.809, P = 0.011) in single-gene analyses. The pairwise linkage disequilibrium (LD) test was found to be in significant LD (D´ = 0.958) between ACE T2547C and I/D polymorphisms in our study population. In haplotype and logistic regression analyses, significant OR was also observed for ACE haplotype CD within the ADD1 460 T carriers in the female group (OR, 1.334; 95% CI, 1.004-1.772, P = 0.047). Interestingly in males, the group with ACE haplotype CD had significantly low incidence of hypertension in the presence of the ADD1 460 TT homozygosity in males (OR, 0.530; 95％ CI, 0.328-0.859, P = 0.010). These findings suggest that the ACE gene polymorphisms may be associated with some determinants increasing BP, and imply an interaction between ACE and ADD1 gene polymorphisms is a positive genetic risk factor for EH in females.