Mexican nationals in Mexico City and Mexican Americans in San Antonio, Tex, have a lower adjusted prevalence of hypertension than San Antonio non-Hispanic whites, especially after adjusting for the greater obesity of San Antonio Mexican Americans. The concomitant examination of a new study from Spain may better explain the association of genetic and environmental factors with hypertension. Three population-based epidemiological studies conducted in Mexico City, Spain, and San Antonio, Tex, were available for comparisons. Hypertension was defined as systolic blood pressure > or = 140 mm Hg, diastolic blood pressure > or = 90 mm Hg, or the use of antihypertensive medications. The prevalence of hypertension was independently associated with age, body mass index, glucose tolerance, and alcohol consumption, with comparable degrees of relationship in all 4 populations. Relative to San Antonio non-Hispanic whites, an excess prevalence of hypertension was observed in Spaniards (odds ratio [OR], 1.53; 95% confidence interval [95% CI], 1.24 to 1.90). A deficit in hypertension prevalence was statistically significant in Mexican nationals (OR, 0.67; 95% CI, 0.53 to 0.85) and close to significance in San Antonio Mexican Americans (OR, 0.86; 95% CI, 0.71 to 1.03). Thus, obesity, educational attainment, type 2 diabetes, glucose tolerance, and marked alcohol consumption (> or = 14 drinks/wk) do not fully explain the increased prevalence of hypertension in Spain and the lower prevalence of hypertension in Mexican-origin populations. Although we cannot conclude definitively that these differences are genetically driven, our results suggest no relationship between Spanish genetic admixture and the deficit in hypertension prevalence in Mexican-origin populations.