We studied the effect of aspirin and sulfinpyrazone on changes in platelet count, thromboxane B2 production, and pulmonary vascular resistance following the onset of veno-venous membrane oxygenator perfusion in sheep. Perfusion under identical circumstances was performed in three groups of animals, with one group serving as controls, one group receiving pretreatment with 1.5 grams of sulfinpyrazone iv, and one group receiving pretreatment with aspirin 50 mg/kg, iv. Both aspirin and sulfinpyrazone eliminated the rise in thromboxane B2 and the increase in pulmonary vascular resistance seen in control animals. Platelet preservation was improved significantly with sulfinpyrazone pretreatment, but not affected by aspirin. We conclude that sulfinpyrazone and aspirin have different mechanisms of action as far as platelet preservation during extracorporeal perfusion is concerned. The major difference may be sulfinpyrazone's ability to reduce platelet adhesion to the membrane surface. Since both aspirin and sulfinpyrazone eliminated the pulmonary vascular-response, but only sulfinpyrazone preserved platelets, it is apparent that the pulmonary vascular response is more closely related to thromboxane synthesis than to platelet disappearance.