BACKGROUND Vasodilator therapy is frequently needed to treat pulmonary hypertension after heart transplantation. In the present study, the effects of intravenous sodium nitroprusside, prostacyclin, prostaglandin E1, and inhaled nitric oxide (5, 10, and 20 parts per million) on central hemodynamics, right ventricular function, and pulmonary selectivity were evaluated shortly after heart transplantation. METHODS Hemodynamic measurements were made after surgery in the intensive care unit. The intravenous vasodilators were compared at equipotent infusion rates. Effects of inhaled nitric oxide were measured after 10 minutes inhalation at each dose level. RESULTS Cardiac output, stroke volume, right ventricular end-diastolic volume, and central filling pressures were highest with prostacyclin (16 +/- 2 ng/kg/min) compared with both prostaglandin E1 (202 +/- 27 ng/kg/min) and sodium nitroprusside (1.0 +/- 0.2 microgram/kg/min). Systemic and pulmonary vascular resistance were lowest with prostacyclin. None of the intravenous vasodilators induced a selective pulmonary vasodilation. In contrast, nitric oxide inhalation induced a selective decrease in pulmonary vascular resistance, with no change in systemic vascular resistance. Cardiac output increased with nitric oxide, whereas mean pulmonary arterial pressure, transpulmonary pressure gradient, and central venous pressure decreased, with the most pronounced effect at an inhaled concentration of 20 parts per million. CONCLUSIONS Prostacyclin is the best choice for intravenous vasodilator therapy after heart transplantation. However, inhaled nitric oxide is the only selective pulmonary vasodilator, which should be used in cases of pulmonary hypertension and severe right ventricular failure associated with systemic hypotension.