In the complex setting of cardiac surgery and cardiopulmonary bypass, several potent mediators are released that by interacting may cause clinical syndromes like coronary ischemia, systemic hypertension, pulmonary hypertension, and renal failure. One of the mediators is serotonin, released from aggregating platelets, and causing vasoconstriction by activating S2-serotonergic receptors, particularly in patients with an impaired endothelial function, as in atherosclerosis. The most important available specific S2-serotonergic receptor antagonist is ketanserin. If administered during or after cardiac surgery, ketanserin lowers systemic and pulmonary blood pressure, and improves peripheral and pulmonary perfusion without causing reflex tachycardia or an increase in pulmonary shunt fraction.