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Pharmacogenetic investigation seeks to identify genetic factors that contribute to interpatient and interdrug variation in responses to antihypertensive drug therapy. Classical studies have characterized single gene polymorphisms of drug metabolizing enzymes that are responsible for large interindividual differences in pharmacokinetic responses to several antihypertensive drugs. Progress is being made using candidate gene and genome scanning approaches to identify and characterize many additional genes influencing pharmacodynamic mechanisms that contribute to interindividual differences in responses to antihypertensive drug therapy. Knowledge of polymorphic variation in these genes will help to predict individual patients’ blood pressure responses to antihypertensive drug therapy and may also provide new insights into molecular mechanisms responsible for elevation of blood pressure.