—Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (≥5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [≤88 mmol/d Na⁺] and high salt [>190 mmol/d Na⁺] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7±107.5 mmol/d urinary Na⁺) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1±50.8 mmol/d Na⁺); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, −3.6/−1.6 mm Hg; white, −6.2/−3.9 mm Hg; Hispanic, −8.1/−5.3 mm Hg) than did enalapril-treated patients (black, −9.0/−5.3 mm Hg; white, −11.8/−7.0 mm Hg; Hispanic, −11.1/−5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.