Brain-derived neurotropic factor (BDNF) is a member of the nerve growth factor family that is important for neuronal survival and plasticity. We recently demonstrated that stress decreases BDNF messenger RNA (mRNA) levels in the hippocampus, which raises the possibility that BDNF may play a role in regulation of the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine whether BDNF expression is present and influenced by stress in other brain areas relevant to control of the hypothalamic-pituitary-adrenal axis. Using in situ hybridization, we found that BDNF mRNA is present in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), the lateral hypothalamus, and the anterior and neurointermediate lobes of the pituitary in rats. Acute (2-h) or repeated immobilization stress increased BDNF mRNA in all of these areas. This was in distinct contrast to stress-induced decreases in extrahypothalamic areas, including the basolateral amygdala, claustrum, and cingulate cortex as well as the hippocampus. BDNF was expressed in both CRF and TRH neurons in the PVN. Reducing glucocorticoid or thyroid negative feedback increased BDNF mRNA in the PVN and anterior pituitary, but not in the neurointermediate lobe. These results suggest that BDNF is a stress-responsive intercellular messenger that may be an important component of the stress response.