The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins’ solution. Group 1 (n=5) received pretreatment with 30 ng/kg/min of PGI2 by infusion and as an additive to the flush (20 µg/L). Group 2 (n=5) received no PGI2 and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies. PGI2 therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2 at 1 and 4 hr, respectively; PGI2: 145 mmHg ±17.0 and 114±11.2; no PGI2: 59 mmHg ±5.8 and 51±4.5; P<0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2 ±91; no PGI2: 1239±68; P <0.05) and lower lung weight (PGI2: 76 g ±4; no PGI2: 146±10; P<0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2 group (increase in % neutrophils; PGI2: 50.4±6.7; no PGI2: 76.9±6.0; P<0.05). Lung injury score assessed by electron microscopy was lower in the PGI2 group (PGI2: 5.2±1.1; no PGI2; 8.1±0.5;.P<0.05). It is concluded that PGI2 treatment is protective against ischemic lung injury in this model.