Epidemiological studies report that quercetin, an antioxidant flavonol found in apples, berries, and onions, is associated with reduced risk of coronary heart disease and stroke. Quercetin supplementation also reduces blood pressure in hypertensive rodents. The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated. We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients. We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress. Men and women with prehypertension (n = 19) and stage 1 hypertension (n = 22) were enrolled in a randomized, double-blind, placebo-controlled, crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo. Blood pressure (mm Hg, systolic/diastolic) at enrollment was 137 +/- 2/86 +/- 1 in prehypertensives and 148 +/- 2/96 +/- 1 in stage 1 hypertensive subjects. Blood pressure was not altered in prehypertensive patients after quercetin supplementation. In contrast, reductions in (P < 0.01) systolic (-7 +/- 2 mm Hg), diastolic (-5 +/- 2 mm Hg), and mean arterial pressures (-5 +/- 2 mm Hg) were observed in stage 1 hypertensive patients after quercetin treatment. However, indices of oxidant stress measured in the plasma and urine were not affected by quercetin. These data are the first to our knowledge to show that quercetin supplementation reduces blood pressure in hypertensive subjects. Contrary to animal-based studies, there was no quercetin-evoked reduction in systemic markers of oxidative stress.