Endothelins are a newly described peptide family consisting of three peptides (ET-1, ET-2 and ET-3) which are the most potent vasoconstrictive peptides known. They are crucial in the regulation of vascular smooth muscle tone. The diverse functions of endothelins are thought to be mediated by interaction with many different receptors coupled to the inositol phosphate/calcium ion messenger pathway. However, because of the structural resemblance of the three peptides, the presence and nature of multiple endothelin receptors remain to be elucidated. We report here the cloning of a complementary DNA encoding a bovine endothelin receptor, which has a transmembrane topology similar to that of other G protein-coupled receptors and shows specific binding, with the highest selectivity to ET-1 in animal cells transfected with the cloned cDNA. This receptor messenger RNA is widely distributed in the central nervous system and peripheral tissues, particularly in the heart and lung. Our results support the view that there are other receptor subtypes.