Recent studies have described a linkage between angiotensin converting enzyme (ACE) gene polymorphism and hypertension in a large number of hypertensive sibs. Moreover, among Japanese, the DD genotype of the ACE gene has been reported to be a genetically predisposing factor for hypertension in a large general population. However, there is some controversy regarding the association between the ACE insertion/deletion (I/D) polymorphism and systemic hypertension. Therefore, we examined the influence of the ACE I/D polymorphism in a random Japanese population. The participants were 2,892 subjects (1,110 males: mean age, 58.4 +/- 15.5; 1,782 females: mean age, 56.2 +/- 15.7) who underwent medical examinations in 1999 in Shigaraki, a suburban town located in an urban area in Shiga prefecture. Among them, 2,395 subjects (917 males: mean age, 58.0 +/- 15.7; 1478 females: mean age, 56.3 +/- 15.6) who gave their informed consent for genetic analysis were enrolled in the present study. Every year since 1991, we have repeatedly performed medical examinations in Shigaraki. ACE genotypes were determined by polymerase chain reaction (PCR) methods. Logistic analysis revealed that age (p < 0.001; odds ratio = 1.091), body mass index (BMI) (p < 0.001; odds ratio = 1.211), and family history of hypertension (p < 0.001; odds ratio = 0.371) were associated with hypertension (systolic blood pressure greater than 140 mmHg and diastolic greater than 90 mmHg). There was no association between ACE polymorphism and blood pressure. There were also no significant differences in blood pressure among males or females across the three genotypes. Moreover, in an analysis of 1,484 subjects (549 males: mean age, 62.8 +/- 12.1; 935 females: mean age, 61.2 +/- 12.6) who were followed-up since 1991, there was no association between ACE polymorphism and changes in blood pressure (p = 0.3905). We conclude that ACE polymorphism does not appear to have any significant association with blood pressure, changes in blood pressure or sex in Japanese subjects, who have a more homogeneous genetic background than any other group reported to date.