The effect of blood activation on lung reperfusion injury during cardiopulmonary bypass was investigated in 20 dogs with the use of a bubble oxygenator (n = 10) or a membrane oxygenator (n = 10). In the bubble oxygenator group, significant leukocyte and platelet right to left atrium gradients were found 15 minutes after lung reperfusion (p less than 0.05, p less than 0.01) accompanied by a sharp increase in plasma malondialdehyde concentration 5 minutes after lung reperfusion, whereas no significant right to left atrium gradient of leukocytes or platelets nor significant increase in plasma malondialdehyde concentration was observed in the membrane oxygenator group. In both the bubble oxygenator and membrane oxygenator group, similar mild to moderate lung histological changes were found before lung reperfusion. After lung reperfusion, however, more endothelial cell swelling (p less than 0.05), leukocyte (p less than 0.01) and platelet (p less than 0.01) accumulation in lung capillaries, leakage of erythrocytes into the alveolar space (p less than 0.05), and type I cell damage (p less than 0.05) were found only in the bubble oxygenator group. Eventually, a significantly higher lung water content was found in the bubble oxygenator group than in the membrane oxygenator group (p less than 0.01) after cardiopulmonary bypass. This study indicated that lung injury during cardiopulmonary bypass starts mainly after lung reperfusion, which was correlated with lung leukocyte and platelet sequestration associated with different types of oxygenators.