The acute hemodynamic effect of intravenous ketanserin, an S2-serotonergic receptor antagonist, was evaluated during right heart catheterization in 20 patients with primary pulmonary hypertension. Pulmonary and systemic vascular resistance and pressure and cardiac output were measured before and after infusion of low and high dose ketanserin. A small decrease in pulmonary vascular resistance occurred after high dose drug infusion (28.4 to 25.0 U X m2; P less than 0.001), and mean pulmonary arterial pressure was unchanged. Decreases in systemic arterial pressure (91.9 to 85.9 mm Hg; P less than 0.0005) and systemic resistance (46.2 to 38.6 U X m2; P less than 0.001) were more pronounced. Cardiac index increased significantly (2.16 to 2.42 l/min/m2; P less than 0.01) due to reduced ventricular afterload. This study indicates that ketanserin has a small pulmonary vasodilating effect in primary pulmonary hypertension of doubtful clinical significance, similar to conventional vasodilators.