1. Corticotropin-releasing factor (CRF) plays a major role in the endocrine, autonomic and behavioral responses to stress. The distribution of CRF and CRF receptors in hypothalamic and extra-hypothalamic brain regions is consistent with its stress-related functions. 2. In most brain regions, CRF acts primarily, if not exclusively, through activation of the adenylate cyclase systems. 3. While previous studies have demonstrated the prenatal presence of CRF receptors, in the early postnatal period the abundance of CRF receptors relative to the magnitude of CRF-stimulated cAMP production suggests that CRF receptors are not fully linked to adenylate cyclase. 4. Because of our interest in the possible involvement of CRF signal transduction in the development of the neonatal stress response, we have examined postnatal development of CRF receptors in relation to adenylate cyclase activity in the rat. 5. CRF binding decreased significantly in the hippocampus and striatum from postnatal days 7-21. Basal adenylate cyclase activity peaked in the second-third week of postnatal life in each brain region. Preliminary studies suggest that early stress can alter the maturation of second messenger systems in the frontal cortex.