Regional hemodynamic responses to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, were compared with those to endothelin (ET) using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of these agents (16 and 160 mmol/kg of L-NMMA and 0.1 or 0.5 nmol/kg of ET-1) dose-dependently increased the blood pressure to the similar level. The cardiac index markedly decreased with ET-1, but was not greatly influenced by L-NMMA. Coronary and cerebral blood flow were not affected by these agents. ET-1 increased the bronchial arterial flow, and markedly decreased the flow in the other organs and tissues examined. L-NMMA almost homogeneously increased the regional vascular resistance to the lesser extent compared to ET-1. Although both ET-1 and nitric oxide are produced in the same cells and exhibit interrelationships, the present results indicate that the regional vascular effects of these agents are different: (a) ET-1 preferentially constricts arteries in all organs and tissues except the lung (where it increases flow) and the heart and brain where it has no wasted effects, leading to reduction in cardiac output, and (b) nitric oxide dilates arteries predominantly in the kidneys, muscle, and white adipose tissues.