CRF in the central nervous system appears to hve activating properties on behavior and to coordinate behavioral responses to stressors. These behavioral effects of CRF appear to be independent of the pituitary-adrenal axis and can be reversed by CRF antagonists. CRF antagonist administration reverses not only decreases in behavior associated with stress, but also increases in behavior associated with stress, thus suggesting that the role of CRF is stress dependent and not intrinsic to a given behavioral response. Further, microinjection of alpha-helical CRF 9-41 and immunotargeting of CRF neurons in separate brain compartments reveal a link between the anatomical sites that contain CRF and the nature of the behavioral response to stressors that can be modified by suppression of endogenous CRF activity therein. These actions of CRF in coordinating coping responses to stress at several bodily levels are consistent with a role for CRF similar to the dual role of other hypothalamic releasing factors in integrating hormonal and neural mechanisms by acting both as secretagogues for anterior pituitary hormones and as extrapituitary peptide neurotransmitters. Moreover, dysfunction in such a fundamental homeostatic system may be the key to a variety of pathophysiological conditions including mental disorders.