An impaired synthesis of nitric oxide (NO) by the vascular endothelium has been implicated in the pathogenesis of essential hypertension (EH). The possible association between a variable number of tandem repeats (VNTR) polymorphism in intron 4 of the endothelial constitutive NO synthase (ecNOS) gene and EH in Japanese subjects was investigated. A total of 123 individuals with EH and 120 normotensive control subjects were studied. The VNTR region of the ecNOS gene was amplified by the polymerase chain reaction to determine the number of repeats, and the allele frequencies were compared between the hypertensive and normotensive groups. Two alleles, containing four and five repeats, were identified. The overall distributions of allele frequencies differed significantly between the two groups, with the four-repeat allele more frequent in the EH group than in the normotensive group (P = .00027, odds ratio = 4.0). The four-repeat allele of the ecNOS gene was thus associated with EH and may be a genetic marker of this disease in Japanese subjects.