Cardiopulmonary bypass is associated with a whole body inflammatory reaction. Exhaled nitric oxide increases in inflammatory lung conditions (eg, asthma) in proportion to the severity of inflammation, and has been proposed as a marker of pulmonary inflammation during cardiopulmonary bypass. This study evaluated the effect of arterial line leukocyte depletion during cardiopulmonary bypass on the rate of alveolar production of exhaled nitric oxide. One hundred and ten patients with normal respiratory function, undergoing first time coronary artery bypass grafting, were randomized to two groups. Fifty-five patients had an arterial line leukocyte-depleting filter and 55 controls had a standard arterial line filter. Nitric oxide was sampled through an endotracheal Teflon tube after median sternotomy, but before cardiopulmonary bypass and 30 minutes after cardiopulmonary bypass, using a real time chemiluminescence analyzer, during the phase of the alveolar plateau. There were no significant differences in the precardiopulmonary bypass values of exhaled nitric oxide between the control (2.92 ± 1.51 ppb/s) and the leukodepletion group (3.11 ± 1.53 ppb/s) (p = 0.4). After cardiopulmonary bypass, the rate of alveolar production of exhaled nitric oxide increased in both groups, being, however, significantly higher in the control group (4.68 ± 1.89 vs 3.72 ± 1.33 ppb/s) (p = 0.02). Continuous arterial line leukocyte-depletion significantly reduces the rate of alveolar production of exhaled nitric oxide after cardiopulmonary bypass. Changes in the rate of alveolar production of exhaled nitric oxide may be used as a marker of pulmonary inflammation in coronary artery surgery.