Despite significant advances in organ procurement and preservation techniques, transplanted lungs are unusually sensitive to ischemia-reperfusion injury. Severe early graft dysfunction has been reported in up to 20% of lung recipients, and this early dysfunction can lead to an increase in early and late morbidity and mortality. Although ischemia plays an important role in initiating early post-transplant lung injury, reperfusion mechanisms are equally important. Pulmonary ischemia-reperfusion (I/R) injury is a complex process involving many cell types and inflammatory biochemical mediators. The study by Sunose and colleagues has utilized a popular dog model of lung transplantation to evaluate the effect of a COX-2 inhibitor on subsequent graft function after 12 hours of ischemia and varying times of up to 4 hours of reperfusion. The hilum of the contralateral non-transplanted lung was ligated in order to evaluate the function of the transplanted organ and its ability to support the animal. The COX-2 inhibitor was administered to both the donor animal 15 minutes prior to lung ischemia, and to the recipient animal 15 minutes prior to reperfusion. COX-2 is an inducible protein that catalyzes arachidonic acid to several active metabolites, including pro-inflammatory thromboxane A2 (TxA2). The authors point out that COX-2 is temporarily induced in monocytes and tissue macrophages during inflammatory conditions, such as might be encountered during ischemia and reperfusion. Therefore, the authors imply that donor pulmonary macrophages may play an important early role in ischemia-reperfusion injury.