Lung resection may be complicated by postpneumonectomy pulmonary oedema. Oxidant generation following surgery-induced ischaemia-reperfusion may be responsible. This hypothesis was tested utilizing isolated, in situ, blood perfused rodent lungs subjected to continuous perfusion (control subjects); one lung ventilation followed by pneumonectomy (group 1); or one lung ventilation followed by reinflation of the collapsed lung (group 2). In control subjects, no significant changes in markers of oxidant damage, oxygenation, pulmonary artery pressure or extravascular albumin extravasation were detected. In group 1 lungs, hydroxyl radical-like damage was detected in association with impaired oxygenation (p<0.05), and increased pulmonary artery pressure and extravascular albumin accumulation in both lungs. In group 2, there was evidence of hydroxyl radical-like damage, and a fall in oxygenation (p<0.05) occurred during one lung ventilation. There was a transient rise in pulmonary artery pressure following lung reinflation and extra vascular albumin accumulation was significantly increased in both lungs (right>left, p<0.05). Both changes were attenuated (p<0.05) following treatment with the reactive oxygen species (ROS) scavenger superoxide dismutase (group 2a) and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (group 2b). Hydroxyl radical-like damage was undetectable following nitric oxide synthase inhibition. Oxidant stress may contribute to the pathologies seen in this model of lung injury.