Prostanoids are a series of arachidonic acid metabolites produced by the action of cyclooxygenase and subsequently by isomerases and synthases. Cells rapidly secrete prostanoids after synthesis, whereupon the prostanoids bind to a family of 8 GPCRs to exert their biological effects. The prostaglandin PGE2 causes pain, vasodilatation, immunosuppression of T cells, bone resorption and promotion of carcinogenesis. Four related GPCRs, EP1, EP2, EP3 and EP4, each bind to PGE2, but the different G protein coupling status of each receptor leads to distinct biological effects. Further diversity is generated by alternative splicing; the human gene for EP3 generates 9 alternatively spliced mRNAs encoding 8 isoforms of EP3. These isoforms of EP3 vary in sequence at their C-termini, and differ in their ability to couple to Gs, Gq or Gi. EP3 is required for fever induced by pyrogens, a response long attributed to prostaglandins by the antipyretic action of aspirin and other COX inhibitors. In animal models of allergy, PGE2-mediated activation of EP3 inhibits inflammation to counteract the allergy-promoting activity of PGE2.