Despite the attenuated skeletal muscle proteolysis that occurs following hypothermic anesthesia and open heart surgery, blood amino acid levels are maintained, suggesting enhanced amino acid release by another organ. To investigate the role of the lung in this response, we determined the release of glutamine (Gln) and alanine by the lung, since these two amino acids transport two-thirds of circulating amino acid nitrogen. Three groups of patients were studied: (a) preoperative non-stressed controls; (b) postoperative general surgical patients; and (c) postoperative cardiac surgical patients studied on Postoperative Day 1 following open heart surgery requiring cardiopulmonary bypass and hypothermic anesthesia. In preoperative controls the lung was an organ of glutamine and alanine balance. These exchange rates were unaffected by the stress of an abdominal surgical procedure despite a mild increase in pulmonary blood flow. However, lung Gln release in the cardiac surgical patients was significantly increased (-0.6 +/- 1.2 mumole/kg/min in controls vs -6.5 +/- 1.3 mumole/kg/min in postoperative hearts, P less than 0.05) and was due exclusively to an increase in the pulmonary artery-systemic arterial concentration difference. Alanine release by the lungs was also increased in the postoperative cardiac surgical patients. The mechanism by which this augmented pulmonary glutamine release occurs following open heart surgery is unclear, but the lungs appear to play a central role in maintaining amino acid homeostasis. This metabolic role of the lungs following hypothermic anesthesia and cardiopulmonary bypass has not been previously described.