Impaired endothelial function with decreased nitric oxide production is shared by insulin resistance and essential hypertension. Although there are limited data on the association between the endothelial nitric oxide synthase (eNOS) G894T polymorphism and hypertension, information is absent on the combined effects of eNOS G894T genotype and insulin resistance status on blood pressure (BP) levels and the familial risk of hypertension. This aspect was examined in a community-based sample of 1021 unrelated African American and white young adults aged 19 to 38 years. African Americans displayed a lower frequency of the T894 allele than whites (0.105 v 0.324, P < .001). After adjusting for sex, age, and body mass index (BMI), noncarriers versus carriers of the T894 allele had significantly higher systolic (SBP), diastolic (DBP) BP and mean arterial pressure (MAP) levels (111.7 v 109.2 mm Hg for SBP; 73.6 v 72.3 mm Hg for DBP; 86.3 v 84.6 mm Hg for MAP), with both African Americans and whites showing similar trends. This association was modulated by insulin resistance status, measured by the homeostasis model assessment of insulin resistance (HOMA IR) using fasting insulin and glucose. Subjects with high insulin resistance (above the median HOMA IR) showed significantly greater differences in BP levels between noncarriers and carriers of the T894 allele. Furthermore, the G894T genotype and insulin resistance also showed a combined effect on the prevalence of parental hypertension, a measure of familial risk, with noncarriers versus carriers in the high insulin resistance group showing higher prevalence (70.5% v 51.3%, P = .006, adjusted for race). Thus, the allelic variation (G894T) in the eNOS gene locus in conjunction with insulin resistance may be one factor contributing to the predisposition to hypertension.