The release of platelet-derived vasoactive substances, particularly serotonin (5-HT), have been implicated in the pulmonary vasoconstrictor response following acute pulmonary embolism. Therefore, we studied the effects of infusing ketanserin, a 5-HT blocking agent, upon pulmonary and systemic hemodynamics and gas exchange in 10 patients with severe acute pulmonary embolism. These patients evidenced 45 +/- 17% mean angiographic pulmonary vascular obstruction. Ketanserin significantly decreased the mean pulmonary arterial pressure from 26 +/- 6 to 23 +/- 5 mm Hg (p less than 0.001). The total pulmonary vascular resistance decreased from 9.1 +/- 3.2 to 8.3 +/- 2.5 mm Hg/L X min X m2 (p less than 0.001). However, the mean cardiac index was unchanged. The systemic arterial and right atrial pressures were significantly decreased after ketanserin. The PaO2 increased in all patients from 60.5 +/- 12.6 to 66.5 +/- 13.6 mm Hg (p less than 0.05), whereas the venous admixture was unchanged. This was attributed to an increased PVO2 (27 +/- 7 to 30 +/- 5 mmHg, p less than 0.01) secondary to a reduction of calculated peripheral oxygen consumption during ketanserin infusion. The results indicate ketanserin is a mild pulmonary vasodilator and can reduce the pulmonary hypertension and increase the PaO2 after pulmonary embolism.