Increased release of serotonin (5-hydroxytryptamine, 5-HT) can play a significant role in the development of acute respiratory failure. The hemodynamic effects of ketanserin, a selective inhibitor of 5-HT2 receptors, were studied in eight patients who developed acute respiratory insufficiency after an episode of circulatory shock. Administration of ketanserin was associated with reductions in systemic and pulmonary artery pressures, without significant change in heart rate or cardiac output. Concomitant decreases in hemoglobin and protein concentrations suggested an associated increase in plasma volume. These changes were attributed to an increased peripheral pooling of blood related to vasodilation. Arterial oxygenation and pulmonary shunt were unaffected. These results indicate ketanserin represents a promising vasoactive agent for treatment of acute respiratory failure in critically ill patients.