OBJECTIVE To determine the direct effect of nicardipine on the pulmonary vascular bed of the intact-chest, spontaneously breathing cat, and to compare its effectiveness as a pulmonary vasodilator with the effectiveness of isoproterenol, nitroglycerin, and sodium nitroprusside. METHODS Prospective, controlled animal study. Each animal received all drugs in random order. METHODS Animal laboratory at a university. METHODS Experiments were performed in vivo in ten intact-chest, spontaneously breathing cats with controlled pulmonary blood flow and constant left atrial pressure, during conditions of increased pulmonary vascular tone. METHODS Five animals received intralobar injections of nicardipine (0.1 to 100 micrograms), nitroglycerin (0.1 to 10 micrograms), sodium nitroprusside (0.1 to 100 micrograms), and isoproterenol (0.01 to 1 microgram). Injections were made only when lobar arterial pressure had returned to baseline value. In another five animals, nicardipine, nitroglycerin, and sodium nitroprusside were administered intravenously as a continuous drug infusion in incremental doses titrated to produce a 20% reduction in mean systemic arterial pressure. Each dose was infused until lobar and systemic arterial pressures stabilized. A minimum, 30-min interval was allowed between the infusions of these drugs. RESULTS When pulmonary vascular tone was increased with a thromboxane A2 mimetic (analog), U46619 (a stable prostaglandin endoperoxide analog), intralobar injections of nicardipine caused dose-related decreases in lobar arterial pressure without affecting left atrial pressure. When compared with the other vasodilator agents, the order of potency was isoproterenol >> nitroglycerin > nicardipine = sodium nitroprusside. Isoproterenol reduced mean systemic arterial pressure 10 to 100 times greater than nitroglycerin, nicardipine, or sodium nitroprusside. However, there were no significant differences between the latter three drugs in producing a decrease in mean systemic arterial pressure. When infused intravenously, nitroglycerin caused the largest amount of pulmonary vasodilation for a given amount of systemic vasodilation. There were no significant differences between the pulmonary vasodilator responses of nicardipine and sodium nitroprusside. CONCLUSIONS In this feline model of increased pulmonary vascular resistance, nicardipine exerts a direct vasodilator effect in vivo on the pulmonary vascular bed. Nicardipine, nitroglycerin, and sodium nitroprusside caused similar decreases in systemic arterial pressure. However, the pulmonary vasodilator effect was greater with nitroglycerin, which suggests that nitroglycerin is more vasoselective for the pulmonary vascular bed than nicardipine or sodium nitroprusside.