Abstract Background. The present pilot study was conducted to evaluate the effect of isolated short-term lung perfusion during cardiopulmonary bypass (CPB) on inflammatory response and oxygenation. Methods. A total of 24 patients undergoing elective cardiac surgery with routine CPB were prospectively assigned to three groups. Group I (n = 7), control subjects receiving neither lung perfusion nor ultrafiltration; group II (n = 9), patients undergoing lung perfusion; and group III (n = 8), patients undergoing lung perfusion plus ultrafiltration. Lung perfusion consisted of single-shot hypothermic pulmonary artery perfusion with oxygenated blood. Proteins indicative of leukocyte activation and lung injury were measured in plasma and bronchoalveolar lavage fluid (BALF). The alveolar-arterial oxygen gradient (A-aD o 2) and the oxygenation index (P o 2/Fi o 2) were also determined. Results. Oxygenation values were best preserved in group III, followed by group II. After CPB, elastase-α 1-proteinase inhibitor complex had increased in plasma in all groups; in BALF it increased in groups I and II, but not in group III. α 2-Macroglobulin increased significantly in BALF in group I but not in groups II and III. Conclusions. These preliminary results provide some evidence that single-shot hypothermic lung perfusion with oxygenated blood at the beginning of CPB may have a protective effect on the lungs, especially when combined with ultrafiltration.