Endothelial dysfunction is observed in the peripheral vasculature of hypertensive patients, but it is unclear how the cerebral circulation is affected. More specifically, little is known about the impact of human hypertension on vertebral artery (VA) endothelial function. This study evaluated whether the endothelial function of the VA is impaired in hypertensive men. For 13 male hypertensive subjects (46 ± 3 yr) and eight age-matched male controls (46 ± 4 yr), blood pressure (BP; photoplethysmography), VA, and common carotid (CC) blood flow (duplex ultrasound) were determined at rest and during 30 min of intravenous l-arginine (30 g; a precursor of nitric oxide) or isotonic saline infusion. Controls and hypertensive subjects demonstrated a similar resting CC (601 ± 30 vs. controls 570 ± 43 ml/min; P = 0.529) and VA blood flow (119 ± 11 vs. controls 112 ± 9 ml/min; P = 0.878). During administration of l-arginine, CC blood flow increased similarly between groups (hypertensive 12 ± 3%, controls 13 ± 2%; P = 0.920). In contrast, the increase in VA blood flow was nonexistent in the hypertensive subjects (0.8 ± 3% vs. controls: 16 ± 4%; P = 0.015) with no significant change in BP. Both CC and VA flow returned to near-resting values within 30 min after the infusion, and for four hypertensive subjects and three controls, time-control experiments using 0.9% saline did not affect VA or CC blood flow significantly. The results demonstrate endothelial dysfunction in the posterior cerebral circulation of middle-aged hypertensive men.