This study was performed to determine the cardiovascular and respiratory effects of ketanserin, a specffic 5-HT2antagonist, following oleic acid lung injury in anesthetized dogs. Following intravenous administration of oleic acid (0.1 ml/kg) to a control group (N = 7), systemic blood pressure decreased significantly. This lowered level of systemic blood pressure was maintained throughout the experiment. Cardiac output gradually decreased following oleic acid administration, while total peripheral resistance, pulmonary vascular resistance, and pulmonary arterial pressure were increased significantly. In a group treated with intravenous ketanserin (0.16 mg/kg, N = 7) 60 min after the injection of oleic acid, no decrease in cardiac output was seen. The increased total peripheral resistance, pulmonary vascular resistance, and pulmonary arterial pressure following injection of oleic acid also were returned toward preoleic acid levels. However systemic blood pressure showed no significant improvement after treatment with ketanserin nor did ketanserin protect against progressive hypoxemia following pulmonary injury with oleic acid. A progressive increase in hemoglobin concentration was seen after oleic acid in the control group. This recovered toward the preoleic acid level following treatment with ketanserin. The postmortem lung wet-dry weight ratio was significantly lower in the treated group compared with the control group. In conclusion, these data suggest that serotonin may have a role in including cardiopulmonary hemodynamic disturbances and in producing increases in extravascular lung water when pulmonary edema is induced by oleic acid injection in anesthetized dogs.