In all target tissues studied corticotropin-releasing factor (CRF) receptors are coupled to adenylate cyclase, and at least in the pituitary, increases in cyclic adenosine monophosphate (cAMP) are recognized as the major mediator of the cell response. This chapter reviews the knowledge of the properties, distribution, mechanism of action, and regulation of CRF receptors in the different target tissues. Receptors for CRF have been identified and characterized in the pituitary gland from rat and a number of primates. In spite of differences in distribution, the binding properties of CRF receptors are similar in pituitary membranes from rat, marmoset, and cynomolgus monkey. The binding of CRF to pituitary membranes is markedly influenced by guanyl nucleotides. Studies of the physicochemical properties of the CRF receptor have been difficult because of the lability of the receptor. Several studies in rat and monkey pituitary cells have shown that stimulation of adrenocorticotropic hormone release by CRF is accompanied by parallel increases in cAMP production.