Endothelins have recently been associated with hypoxia-related vascular smooth-muscle constriction and with the so-called no-reflow phenomenon following reperfusion. Their action is tissue dependent. The role of endothelins on vascular smooth muscle in bone is unknown. An ex vivo perfusion model was used to investigate the effects of the three different endothelins on the vascular resistance in the canine tibia. Endothelin-1 and endothelin-2 had molar potencies similar to that of norepinephrine, whereas endothelin-3 was less potent. Tachyphylaxis to the same dose of endothelin-1 did not occur. The calcium channel blocker, diltiazem, attenuated (45% reduction) the vasoconstrictor responses to norepinephrine (p < 0.005) but had a smaller effect (24% reduction) on the responses to endothelin (p < 0.025). Vascular smooth muscle in bone appears to have endothelin receptors that are similar to those in other organs.