In a canine model of acute ischemic lung injury, a hypertonic citrate solution (HTC) widely used for renal preservation in the United Kingdom, was compared with modified Euro-Collins’ solution (ECS) currently the most widely clinically used pulmonary perfusate. Ten beagle dogs underwent left thoracotomy and exclusion of the left lung in situ. The lung was flushed with 30 ml/kg of either HTC or ECS and subjected to 60 min of warm ischemia. The circulation to the lung was then restored, the contralateral lung excluded, and the animal ventilated at a fixed FiO2of 0.4 for 4 hr. Lung function was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain, bronchoalveolar lavage, and ultra- structural studies. Flush perfusion with HTC was associated with significantly less severe reperfusion injury, as determined by superior arterial oxygenation (Pa02at 1 hr: HTC—152 mmHg [(95% confidence interval) Cl] [122-182], ECS— 59 [47-70]; PaO2 at 4 hr: HTC—124 [100-149], ECS— 51 [42-61]), lower pulmonary vascular resistance index (PVRI at 4 hrs: HTC—838 dynes sec cm-5m-2[651- 1075], ECS—1233 [963-1588]); and lower lung weight (HTC—85 g [66-107], ECS—146 [114-184]). Bronchoalveolar lavage studies demonstrated an influx of neutrophils following reperfusion that was significantly less marked in the HTC group (increase in % neutrophils: HTC 24 [19-29], ECS 77 [72-82]). Lung injury assessed by electron microscopy tended to be less severe in the HTC animals. We conclude that HTC may offer an alternative superior to ECS for lung preservation.