Background: Hypertension is a risk factor for coronary heart disease (CHD), but the causes of hypertension remain largely unknown. Genetic variation is thought to contribute to the etiology of hypertension. We tested a single-nucleotide polymorphism (SNP) (Lys67Arg, rs197922) in the Golgi SNAP Receptor Complex Member 2 (GOSR2) gene for association with hypertension and blood pressure (BP). We chose this SNP because it was nominally associated with CHD in earlier studies. Further, GOSR2 is located in a linkage region for hypertension and BP in human and animal studies. Methods: We used logistic and linear regression to test associations of the GOSR2 SNP with hypertension and BP among 3,528 blacks and 9,861 whites from the Atherosclerosis Risk in Communities (ARIC) study. Race-specific regression models of hypertension were adjusted for age and gender. Regression models of BP were further adjusted for antihypertensive medication use. Results: The GOSR2 Lys67 allele was associated with hypertension in whites (odds ratio (OR) = 1.09, P = 0.01) but not blacks (OR = 0.96, P = 0.47). The Lys67 allele was associated with increased systolic BP (SBP) in both races (0.87 mm Hg, P < 0.001 among whites and 1.05 mm Hg, P = 0.05 among blacks). A similar association in whites was observed for the GOSR2 SNP and SBP in the Women's Genome Health Study (WGHS) (OR = 1.03, P = 0.04). The OR remained unchanged after adjustment for antihypertensive medication use (OR = 1.03, P = 0.11), though it was no longer statistically significant. Conclusions: We found evidence that a SNP in GOSR2 is modestly associated with hypertension in whites from the ARIC study and the WGHS.