1. Endothelins (ETs) and sarafotoxins (SRTXs) belong to a family of 21-amino-acid peptides comprising at least eight isoforms. 2. ET exerts multiple pharmacological effects through its receptors. 3. This review summarizes the observations and findings pointing to the existence of receptor subtypes and leading to their identification. 4. Two receptor subtypes have been cloned and stably expressed. 5. The existence of at least two more is predicted by dissimilar ligand potencies in different tissues, kinetics of receptor-ligand interactions, and cross-linking of receptors and radiolabeled ligands.