The degree of lung allograft inflation during harvest and storage may affect posttransplantation function. High volume ventilation causes pulmonary vascular injury and increased pulmonary capillary permeability. However, the effect of lung inflation on pulmonary capillary permeability after hypothermic flush and storage is unknown. The current study was designed to examine the effects of hyperinflation and hypoinflation during preservation on pulmonary vascular permeability. Methods: An isolated, ex vivo rabbit lung gravimetric model without the confounding effects of reperfusion was used to determine post pulmonary capillary filtration coefficient (K(f)). New Zealand White rabbits (2.75 to 3.15 kg) were intubated and the lungs ventilated with room air (tidal volume 25 ml). After sternotomy and heparinization, the pulmonary artery was flushed with low potassium dextran-1% glucose solution (200 ml). The heart-lung block was then excised. Two studies were conducted. For measurement of changes in airway pressure and lung volume during preservation, lungs were inflated to one of four storage volumes (12, 25, 40, 55 ml) with room air, 100% O2, or 100% N2 and stored at 10° C in a sealed container filled with saline solution. During preservation, lung volume and airway pressure were measured at 3, 6, 12, and 24 hours. In the K(f) study, lungs were inflated with 100% O2, 50% O2 (with 50% N2), or room air and preserved. After 24 hours of preservation at 10° C, the heart-lung block was suspended from a strain-gauge force transducer and the lungs were ventilated with room air. The pulmonary artery was connected to a reservoir of hetastarch solution (6% hetastarch with 0.9% saline solution). Lung weight gain, airway pressure, pulmonary artery pressure, and heft atrial pressure were measured continuously. After a brief flush with hetastarch solution, the reservoir was then elevated to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. Results: The slope of subsequent steady-state lung weight gain was used to determine the K(f). The current study demonstrated the following: (1) changes in lung volume and airway pressure during storage increased with intraalveolar O2 concentration, (2) irrespective of inflation, fraction of inspired oxygen, hyperinflation during lung preservation increased the K(f) in a volume-dependent fashion; (3) K(f) was increased in lungs stored hypoinflated with room air; and (4) at any inflation volume, the F(f) was significantly increased with 100% O2 inflation after 24 hours of preservation. Conclusion: These results suggest that storage at high lung volume or high inspired oxygen fraction increases pulmonary capillary permeability.