OBJECTIVE To determine effects of surgical pleurotomy, continuous positive airway pressure, and fluid balance during cardiopulmonary bypass (CPB) on lung mechanical properties and indices of oxygenation. METHODS Prospective, descriptive, and interventional study. METHODS Cardiothoracic service at a major university referral center. METHODS Eighteen anesthetized-paralyzed patients undergoing elective coronary artery bypass grafting requiring CPB. METHODS During CPB, continuous positive airway pressure (CPAP) was applied to nine patients, in nine others, no CPAP was applied. RESULTS From measurements of airway and esophageal pressures and flow, lung resistance and elastance were determined before sternotomy and after sternal reapproximation. Measurements were made during forced ventilation over a physiologic range of tidal volumes and frequencies, and frequency and volume dependences of lung resistance and elastance were additionally identified. In all patients, lung resistance and elastance increased after CPB, consistent with models of pulmonary edema. Multiple regression analysis showed that these increases were relatively less in patients with intact pleurae (p < 0.05) or net negative fluid balance (p < 0.05); however, no difference in these increases was noted between patients receiving CPAP and those receiving no CPAP. Increases in lung resistance were positively correlated to net fluid balance, and negatively correlated to frequency and tidal volume (p < 0.05). Increases in lung elastance were positively correlated to tidal volume (p < 0.05). Absolute change in alveolar-arterial oxygen gradient was negatively correlated with net fluid balance, whereas percentage change was positively correlated to changes in lung elastance (p < 0.05). CONCLUSIONS These findings suggest that pleurotomy before CPB and positive fluid balance during CPB enhance postbypass pulmonary edema and/or atelectasis, as demonstrated by acute changes in respiratory mechanics and indices of oxygenation. Low levels of CPAP applied during CPB did not significantly change either mechanical properties or oxygenation.