Reports have shown increased systemic levels of endothelins during coronary artery bypass grafting in human beings. It was not known whether increased endothelin levels during coronary artery bypass grafting reflect a general systemic response to the surgical procedure or increased myocardial production of endothelins in response to ischemia and reperfusion. We therefore measured endothelin levels in the right atrium and proximal aorta of 15 patients undergoing coronary artery bypass grafting for anginal syndrome immediately before aortic crossclamping and again after cessation of cardiopulmonary bypass. In five patients, we also measured coronary sinus levels of endothelins during cardiopulmonary bypass circulation. We found that endothelin levels were elevated throughout the surgical procedure. Right atrial endothelin levels were significantly elevated after cessation of cardiopulmonary bypass circulation with respect to values immediately before aortic crossclamping (11.1 ± 3.1 vs 14.2 ± 3.7 pg/ml, p = 0.008), whereas endothelin levels in the proximal aorta did not rise significantly (10.5 ± 2.3 vs 11.6 ± 2.4 pg/ml, p > 0.5). Coronary sinus endothelin levels tended to decline temporarily during bypass circulation (11.1 ± 2.1 pg/ml before aortic crossclamping, 7.9 ± 1.9 1 minute after release of aortic crossclamp, and 9.9 ± 2.1 pg/ml after release of partial aortic crossclamping, p = 0.06). We conclude that the rise in right atrial endothelin levels during coronary artery bypass grafting reflects systemic production and secretion of endothelins, probably by vasculature or organs distal to the proximal aorta, and is not the result of increased myocardial production and secretion of endothelins.