A defective vascular activity of endothelial vasoactive substances is observed in essential hypertension and hypercholesterolemia, and is believed to participate in the vascular abnormalities characteristic of these conditions. The present study aimed to determine the role of cyclooxygenase (COX) products in the maintenance of vascular tone and in the endothelium-mediated vasodilation of healthy subjects, and to investigate their contribution to the endothelial dysfunction of essential hypertensive and hypercholesterolemic patients. Methods and Results. The effects of intraarterial aspirin (ASA; 1, 3 and 10 mg/min), were assessed on basal forearm blood flow (FBF) (strain gauge plethysmography) and on the responses to acetylcholine (Ach; 7.5, 15 and 30 g/min) and sodium nitroprusside (SNP; 0.8, 1.6 and 3.2 g/min) in 24 normal, 23 hypertensive and 24 hypercholesterolemic subjects. Basal FBF was not different among the 3 groups (p=0.95). ASA resulted in a significant reduction of FBF from baseline in normal (p=0.003), hypertensive (p=0.001), and hypercholesterolemic subjects (p=0.001), without any difference among the 3 groups (p=0.90). ASA significantly improved the effect of Ach in normal (p=0.008), hypertensive (p=0.008), and hypercholesterolemic subjects (p=0.022), without significant difference among the 3 groups (P=0.46). ASA did not significantly modify the vasodilator effect of SNP in any of the 3 groups. Conclusions. These findings suggest that, in humans, vasodilator prostanoids actively contribute to the maintenance of basal vascular tone, while vasoconstrictor products of COX activity limit endothelium-dependent vasodilation. COX products do not appear to play a major role in the endothelial dysfunction of hypertensive or hypercholesterolemic patients.