With the introduction of platelet-activating factor antagonists, a direct inhibition of ischemia-induced reperfusion injury can be achieved by prevention of platelet activation, reduction of microvascular leakage, and platelet-activating factor-induced bronchoconstriction. At present, two preservation methods are established for clinical lung preservation: (1) donor core cooling by extracorporeal circulation and (2) pulmonary artery flush with Euro-Collins solution and prostacyclin. We compared the quality of organ preservation obtained with these methods to the application of a platelet-activating factor antagonist (WEB 2170; 0.3 mg/kg) for the donor, perfusion solution, and throughout the first 6 hours of reperfusion in combination with prostacyclin (20 ng/kg/min) and Euro-Collins solution (60 ml/kg). Eighteen heterotopic heart and orthotopic left lung transplants were performed in three groups of six dogs each after 6 hours of cold ischemia (group I, donor core cooling; group II, Euro-Collins flush and prostacyclin; group III, Euro-Collins flush, prostacyclin, and WEB 2170). Myocardial preservation was achieved with St. Thomas' Hospital solution (20 ml/kg) in all groups. After transplantation, cardiorespiratory function was assessed at an inspired oxygen fraction of 0.4. After transplantation, superior results were observed in group III, as expressed by significantly improved oxygenation, while cardiac output and pulmonary artery pressures were similar in all groups. We concluded that the use of the platelet-activating factor antagonist WEB 2170 resulted in better lung preservation than current clinical standards.