We have identified and characterized cDNAs encoding a novel receptor that is a member of a distinct class of seven transmembrane helix, G(s)-coupled receptors. This receptor mediates ligand-dependent stimulation of intracellular cAMP levels in response to physiologic concentrations of corticotropin-releasing factor (CRF) and to the related frog skin peptide, sauvagine. The pattern of CRF receptor mRNA expression in the brain, pituitary gland, and other organs corresponds precisely to that predicted for the classic CRF receptor, suggesting that this receptor serves to mediate the known biological effects of CRF on behavior, stress, and homeostasis. Alternative splicing events generate a second, relatively abundant gene product expressed in a distinct ontogenic pattern. These findings serve to identify the receptor for an important neuropeptide.