Background. Increased systemic levels of thromboxane (Tx) during cardiopulmonary bypass (CPB) in humans have been reported. It is not known whether this reflects a general systemic response to the surgical procedure or an increased pulmonary production of Tx in response to ischemia and reperfusion. Methods. Thromboxane B2 levels were measured in the right atrium and left atrium of 14 patients undergoing coronary artery bypass grafting for angina. Eight patients (group 1) were without aspirin for at least 15 days before operation, and 6 patients (group 2) were treated with aspirin (100 mg/day) for at least 1 month before operation. Levels of TxB2 were determined by enzyme immunoassay after lipid extraction and separation. Results. Thromboxane B2 levels were elevated throughout CPB. In group 1, left atrial TxB2 levels were significantly higher (p < 0.05) than right atrial levels at all study points during CPB. After pulmonary reperfusion, TxB2 levels in both atria increased significantly (p < 0.02) compared with the levels before cross-clamping of the aorta, and there was an increasing gradient between the two atria (p < 0.05). Mean plasma TxB2 levels during CPB in group 2 were significantly reduced (p < 0.0001) in the right atrium (by 73%) and in the left atrium (by 69%) compared with levels in group 1. Conclusions. The rise in TxB2 levels in the left atrium after CPB in humans reflects production of Tx mainly in the lungs, most probably by ischemic pulmonary tissue and intravascular hematologic components. Aspirin markedly reduces Tx production during CPB, and it might play a major role in preventing pulmonary injury after operations with CPB in humans.