Prostacyclin, a member of the eicosanoid family of lipid mediators, is the major product of arachidonic acid metabolism formed in the marcovascular endothelium. It is a potent vasodilator, antithrombotic, and antiplatelet agent that mediates it effects through a membrane-associated receptor termed the IP. Cloning of the cDNA for IP, from human and other species, indicated its membership of the G protein-coupled receptor superfamily and has allowed detailed examination of the signaling and regulatory pathways utilized by this receptor. This article examines the current state of knowledge of the IP, its signaling and regulation, and its biological role in vivo and examines the possible existence of multiple PGI2 receptor sites.