In normotensive humans, the endothelium modulates vascular tone mainly by the production of nitric oxide. In human essential hypertension the basal release of nitric oxide is reduced and forearm vasodilation to the endothelium-dependent agonists acetylcholine or bradykinin is blunted. Defective basal release of nitric oxide seems to be secondary to blood pressure increase while impaired agonist-evoked endothelium-dependent vasodilation is probably a primary phenomenon. This latter endothelial dysfunction seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of constrictor prostanoids. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensives. In contrast, vasoconstrictor prostanoid production seems to be associated with aging. In essential hypertensive patients, although only scanty data are available, chronic effective pharmacological treatment seems to restore impaired basal production of nitric oxide but does not improve vascular response to endothelial agonists.