The vasoconstrictor effects of endothelin-1 (ET-1) and norepinephrine (NE) were compared in the exteriorized rat mesentery in situ. ET-1 was 1,000 times more potent than NE in constricting both arterioles and venules. Vasoconstrictions induced by ET-1 lasted much longer than those caused by the catecholamine. At nonrelaxant doses, acetylcholine and sodium nitroprusside antagonized the constrictive response of microvessels to ET-1 and NE. However, larger doses of acetylcholine were necessary to inhibit the response to ET-1 than that to NE.