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We have previously shown that porcine endothelin (ET-1) releases endothelium-derived relaxing factor (EDRF) in the rat isolated perfused mesentery. Here we show that both ET-1 (1–100 pmol) and rat endothelin (ET-3, 1–300 pmol) release EDRF in this preparation and that ET-1 releases EDRF from the luminally perfused aorta of the rabbit. Furthermore, we confirm that, as a pressor agent, ET-1 is greater than 10 times more potent than ET-3. Vasodilatations in the rat isolated perfused mesentery in response to ET-1 and ET-3 were due to the release of EDRF since they were inhibited by removal of the endothelium, methylene blue (100$ mUM), or hemoglobin (30$ mUM). ET-3 was more selective than ET-1 as a vasodilator because ET-1 induced vasodilatations were limited and in the higher doses overwhelmed by concurrent vasoconstrictions. Release of EDRF from the rabbit aorta in response to ET-1 but not to …