Nitric oxide (NO), the active moiety of the endothelium-derived relaxing factor (EDRF) that was discovered by Furchgott & Zawadzki (30), serves as an important intercellular mediator in the vasculature. kidney, endocrine system, and central nervous system. Accordingly, NO contributes to the complex regulation of local and systemic vascular resistance, distribution of blood flow and oxygen delivery, sodium balance, and arterial pressure. Excessive NO synthesis may result in systemic hypotension, as in septic shock; conversely, impaired NO synthesis may lead to pathologic vasoconstriction, to tissue ischemia with organ dysfunction, and to the genesis or perpetuation of hyper tension. Although appreciation of the role of NO in integrative cardiovascular physiology is quite recent, a rapidly expanding literature describes its effects in humans and animals. This review focuses on the systemic vascular phar macology of NO, rather than on its important roles in the pulmonary and uteroplacental circulations. citing selected investigations that bear on its role in several aspects of hemodynamic regulation.