The optimal state of inflation for lung allografts during preservation is not known. We previously showed that hyperinflation of canine lung allografts during storage improved posttransplant graft function as measured during 10 minutes of contralateral pulmonary artery occlusion. However, we have also shown that hyperinflation during storage increases pulmonary capillary permeability. It is possible that short-term total cardiac perfusion through the transplanted left lung (for assessment) may not adequately reproduce the clinical situation. The purpose of this study was to assess the effects of hyperinflation during storage in a canine left single- lung transplantation model in which all perfusion was continuously directed to the graft after implantation. Twenty canine left single-lung transplants were done. The lungs of donor animals were ventilated at a tidal volume of 750 ml and an inspired oxygen fraction of 100%. Donor lungs were flushed with modified Euro-Collins solution and the trachea occluded at end inspiration. For donors in groups I and III, the trachea was sealed at that postinflation volume. In groups II and IV, 200 cc air was withdrawn from the endotracheal tube under positive pressure and the trachea scaled at the lower tidal volume. Lungs were then extracted and stored at 1° C for 12 hours. After the preservation period, left lung transplants were performed. After implantation in all groups, the right pulmonary artery was ligated. In groups I and II, the right bronchus was ligated and in groups III and IV the right bronchus was kept open. Subsequent allograft gas exchange and hemodynamics were assessed during a 6-hour period of reperfusion. Alter assessment, both lungs were excised, wet/dry lung weight ratio was calculated, and histologic examination was done. During the 6-hour assessment, lungs stored in a state of hyperinflation (groups I and III) showed rapid deterioration of gas exchange. At the final assessment, arterial oxygen tension and alveolar- arterial oxygen gradient of groups I and III were significantly worse than those of groups II and IV (group I versus group II: arterial oxygen tension 87.5 ± 15.0 versus 373.8 ± 65.5 mm Hg, alveolar-arterial oxygen gradient 564.4 ± 13.2 versus 298.6 ± 69.3 mm Hg, p < 0.05; group III versus group IV: arterial oxygen tension 245.4 ± 33.0 versus 543.6 ± 41.8 mm Hg, alveolar-arterial oxygen gradient 392.5 ± 35.6 versus 120.5 ± 34.7 mm Hg, p < 0.01). We conclude that donor lung hyperinflation during storage does not provide better posttransplant allograft function when perfusion is limited only to the allograft.