Background: We investigated the effect of lazaroid U74389G, a potent inhibitor of lipid peroxidation, on ischemia-reperfusion injury at three different doses in the rat orthotopic left lung transplantation model. Methods: Four groups of reperfused lungs were studied. In group I (control) donor lungs were transplanted after 12 hours of preservation in University of Wisconsin (UW) solution at 4 degrees C. In groups II, III, and IV, lazaroid was used as an additive to UW solution at concentrations of 30 mu mol/L, 50 mu mol/L, and 100 mu mol/L, respectively, and was also administered intravenously to the recipients 30 minutes before reperfusion after 12 hours of storage in the UW solution at 4 degrees C. Results: After 12 hour of reperfusion, gas exchange function (p < 0.01), tissue lipid peroxide levels (p < 0.05) and histologic damage in reperfused lung allografts (p < 0.05) were significantly improved in lazaroid-treated group IV compared with control group I. Conclusions: These findings suggest that lazaroid U74389G ameliorates ischemia-reperfusion injury in rat lung transplants by inhibiting lipid peroxidation.