Areca tannin has been suggested as having a blood pressure regulatory effect through its ability to inhibit the pressor response to both angiotensin I and II. As genetic and environmental factors determine the susceptibility and development of diseases and no report has been published concerning the genetic interaction of metabolic effects in areca nut/betel quid (BQ) chewers, it is proposed that the cardiovascular effects of chronic BQ usage can be affected by the polymorphism of the angiotensin converting enzyme (ACE) gene. This is a cross-sectional community-based study. A total of 189 BQ chewing subjects and 256 non-chewing controls were studied. BQ chewing status was determined by using a structured questionnaire, and insertion/deletion (I/D) polymorphisms were determined by a polymerase chain reaction. BQ chewers with the DD genotype had significantly lower blood pressure, pulse pressure, and prevalence of hypertension compared with those of chewers with II or ID genotypes. Multiple stepwise regression analysis confirmed that the ACE I/D genotype was independently associated with systolic blood pressure (SBP). BQ chewers with the DD genotype accounted for a significant age, sex, and waist-to-hip ratio adjusted decrease in SBP (-5.9 mm Hg, P=0.021). This finding suggests that BQ chewing may be related to blood pressure regulation, which supports the hypothesis that concomitant genetic susceptibility and environmental factors determine the level of blood pressure.