Corticotropin-releasing factor (CRF) receptors have been identified, characterized, and localized in the pituitary gland. This chapter provides a summary of the characteristics of CRF-stimulated adenylate cyclase activity in brain with respect to its pharmacology, regional distribution, and sensitivity to in vitro regulation. In determining an incubation time, it is appropriate to choose a maximal period of time during which CRF stimulation of Cyclic adenosine monophosphate increases linearly with time. Upon establishing appropriate assay conditions, the pharmacology of the receptor mediating the stimulation of adenylate cyclase by CRF was investigated with respect to the activity of various biologically active and inactive CRF-related peptides. The highest concentration of CRF receptors was localized to olfactory bulb followed by cerebral cortex and cerebellum, and progressively lower binding in hypothalamus, striatum, midbrain, hippocampus, and spinal cord, respectively. Gpp(NH)p can also facilitate receptor-mediated inhibition of adenylate cyclase activity for receptors which are coupled in an inhibitory fashion to the catalytic subunit.