To investigate the possible role of endothelin in coronary vasoconstriction contributing to the development of myocardial ischemia, plasma endothelin concentrations at rest and during atrial pacing-induced myocardial ischemia have been measured in blood samples drawn from the aorta and coronary sinus in 12 patients with significant narrowing of the left anterior descending coronary artery. The plasma endothelin concentrations at rest were similar in the aorta (AO/R) and coronary sinus (CS/R) (4.8 ± 2.4 and 4.5 ± 1.7 pg/ml, respectively), the difference between coronary sinus and aorta plasma endothelin concentration (CS/R-AO/R) being-0.3 ± 1.7 pg/ ml. During atrial pacing-induced myocardial ischemia aortic plasma endothelin concentration (AO/P) did not change (4.6 ± 2.6 pg/ml) and only an insignificant increase in the plasma endothelin concentration in the coronary sinus (CS/P) was observed (5.3 ± 2.8 pg/ml). The difference between coronary sinus and aortic endothelin plasma concentration (CS/P-AO/P) was 0.6 ± 2.5 pg/ml. Finally, the difference in endothelin concentrations between coronary sinus and aorta rose only insignificantly during pacing as compared to the resting values ([CS/P-AO/P] – [CS/R-AP/R] being 0.9 ± 3.2 pg/ml). Thus, atrial pacing-induced myocardial ischemia in patients with significant left anterior descending coronary artery stenosis was not accompanied by significant changes in coronary sinus plasma endothelin concentrations. This suggests that increased release of endothelin into plasma is probably not responsible for coronary artery vasoconstriction in patients with significant coronary artery narrowings. However, neither of two other possibilities can be ruled out: that basal level of endothelin secretion is a prerequisite for the effect of another vasoconstrictor or that local intraluminal or abluminal secretion and uptake of endothelin occurs.