Endothelin-1 (ET-l) is an endothelial-derived coronary vasoconstrictor peptide which mediates its actions through the Endothelin-A and the Endothelin-B receptors. The current study was designed to test the hypothesis that at low-dose ET-l to mimic pathophysiologic concentrations, ET-1 mediates coronary vasoconstriction through the ET-A receptor. Therefore, ET-1, (Group 1, n = 5). Sarafotoxin—a specific ET-B receptor agonist (Group 2, n = 5)—each at 2 ng/kg/min were infused into the left circumflex coronary artery in the anesthetized dog. In Group 3 (n = 5) the same dose of ET-1 was infused with 4 μ/kg/min of the specific ET-A receptor antagonist FR 139317. No difference in hemodynamics and coronary blood flow (CBF), coronary vascular resistance (CVR), and coronary artery diameter(CAD) were observed at baseline between the groups, and no alterations in systemic hemodynamics and plasma ET concentrations were observed during the protocol. CBF, CVR, and CAD were determined at baseline and during infusions and were calculated as % change (Δ) from baseline. Group 1 Group 2 Group 3 %ΔCBF -48 ± 7 * -9 ± 3 -12 ± 3 %ΔCVR 105 ± 24 * 24 ± 9 7 ± 6 %ΔCAD 4.6 ± 0.9 * -1.0 ± 0.3 -1.4 ± 0.7 Data are mean ± SEM * p < 0.01 vs. Group 2 and Group 3 This study demonstrates in vivo that: ET-l at pathophysiologic concentrations predominantly induces coronary vasoconstriction via the ET-A receptors at the level of the resistance vessels.