African Americans are a critical population in which to study the impact of physiologically important candidate gene mutations on the occurrence of hypertension. African Americans not only have a higher prevalence of hypertension, but the disease strikes earlier, with greater severity, and often results in death at an earlier age compared with whites in the United States. In this study, 3 physiologically important candidate gene mutations (angiotensinogen A[-6], alpha-Adducin Gly460Trp, and G-Protein beta(3)-subunit C825T) were examined for their association with hypertension status in a sample of 904 African Americans from Jackson, Mississippi. Tests of simple association and multivariate logistic regression analyses revealed no association between hypertension status and any of the studied polymorphisms. This lack of association persisted after stratification of the sample by gender and body size. These data indicate that these polymorphisms do not contribute in a significant way to interindividual variation in the risk of hypertension in this sample of African Americans, and further genome-wide studies should be performed to identify genes that may influence blood pressure levels in this population.