BACKGROUND We have established that thromboxane B2 (TX) blood levels increase across the pulmonary circulation after total cardiopulmonary bypass (CPB) but not after partial CPB. In the present study, we used the same model and examined the parameters of pulmonary injury after total or partial CPB. RESULTS Fourteen anesthetized sheep were placed on total CPB (n = 7), without ventilation and with occlusion of the pulmonary artery, or partial CPB (n = 7), with ventilation and an open pulmonary artery. After 90 minutes, the sheep were separated from CPB, and the pulmonary artery was perfused normally. After 30 minutes, we elevated left atrial pressure in all sheep. Plasma TX, plasma leukotriene B4, platelet counts, white blood cell counts, and plasma protein concentration were measured before CPB and every 15 minutes after CPB for 1 hour. The right and left atrial blood samples were obtained simultaneously. Pulmonary arterial pressure, left atrial pressure, and pulmonary arterial flow were measured. Pulmonary vascular resistance (PVR) was calculated for 30 minutes after CPB. Lung lymph protein, TX, leukotriene B4, and flow were measured before CPB and every 30 minutes after CPB for 1 hour. Pulmonary biopsies and bronchoalveolar lavage fluid were obtained before CPB and at the end of the experiment. After total CPB, levels of TX across the pulmonary circulation increased significantly, but leukotriene B4 remained constant. Platelets and white blood cells were consumed across the pulmonary circuit after total CPB but not after partial CPB. PVR increased by 170%, lymph flow increased by 233%, lung water content increased by 15%, and the ratio of lymph to plasma protein decreased by 20% after total CPB, but similar changes did not occur after partial CPB. CONCLUSIONS During total CPB, the lungs are totally dependent on oxygen supply provided by nonpulsatile bronchial arterial flow. Lung injury seen with restoration of pulmonary artery flow and ventilation may be the result of an inflammatory response associated with TX elevation after a period of relative pulmonary ischemia. Pulmonary injury was not seen after less severe pulmonary arterial flow deprivation, with maintenance of ventilation (partial CPB). Although the specific cause is undetermined from these data, the occurrence of elevated TX levels and lung damage after total CPB is clearly established.