Quercetin (Q) reduces blood pressure (BP) in hypertensive individuals, but the mechanism is unknown. We hypothesized that acute Q aglycone administration reduces BP in hypertensive men by decreasing angiotensin-converting enzyme (ACE) activity and/or by lowering the ratio of circulating endothelin-1 (ET-1) to nitric oxide and that these alterations will improve endothelial function. Using a double-blind, placebo-controlled, crossover design Q or placebo (P) was administered to normotensive men (n = 5; 24 ± 3 years; 24 ± 4 kg/m(2)) and stage 1 hypertensive men (n = 12; 41 ± 12 years; 29 ± 5 kg/m(2)). As anticipated, ingesting 1095 mg Q did not affect BP in normotensive men but resulted in maximal plasma Q (2.3 ± 1.8 μmol/L) at approximately 10 hours, with Q returning to baseline concentrations (0.4 ± 0.08 μmol/L) by approximately 17 hours. Results from this study provided rationale for determining end-points of interest in stage 1 hypertensive men 10 hours after ingesting Q or P. In stage 1 hypertensive individuals, plasma Q increased(0.6 ± 0.4 vs. 0.05 ± 0.02 μmol/L), and mean BP decreased (103 ± 7 vs 108 ± 7 mm Hg; both P < .05) 10 hours after Q vs P, respectively. Plasma ACE activity (16 ± 10 vs 18 ± 10 U/L), ET-1 (1.6 ± 0.9 vs 1.6 ± 0.8 pg/ml), nitrites (57.0 ± 3.0 vs 56.7 ± 2.6 μmol/L), and brachial artery flow-mediated dilation (6.2 ± 2.9 vs. 6.3 ± 3.2%) were unaffected by Q. A single dose of Q aglycone reduces BP in hypertensive men through a mechanism that is independent of changes in ACE activity, ET-1, or nitric oxide bioavailability and without affecting vascular reactivity.