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After 100 years of measurement, reasons for interindividual and populational variation in blood pressure have proven difficult to identify. Use of 24-hr blood pressure monitoring has revealed additional intraindividual variation. Variability in kidney function, extracellular sodium and potassium (Na:K) balance, and factors affecting water, sodium, and potassium resorption obviously affect blood pressure. Alterations in these and additional factors predict development of hypertension. In recent decades the molecular revolution has increased scrutiny of genetic factors contributing to interindividual and populational differences in blood pressure and hypertension. Most investigations across populations and environments have focused on components of the renin-angiotensinaldosterone system. DNA polymorphisms within this system clearly are associated with blood pressure and hypertension; however, these associations tend to vary across race and ethnicity, ecological settings, and sex. There is clear evidence that polymorphisms at the renin, angiotensinogen, and angiotensin-converting enzyme loci influence both blood pressure and hypertension. In addition, evidence suggests gene-gene and gene-environment interactions along with sex-specific actions of these loci on blood pressure.