We propose to isolate, determine the chemical structure and synthesize low molecular weight peptides present in hypothalamic tissue and which regulate the secretion of ACTH and beta-endorphin. The complex of peptides includes two corticotropin releasing factors (CFR's), an inhibitor and a potentiator. We further propose to follow the potency of these peptides using suspension of isolated pituitary cells. These cells respond to addition of CRF with increased secretion of ACTH and of beta-endorphin. The inhibitor reduces, the potentiator enhances, the response of the isolated cells to CRF. We further propose to examine the actions of these peptides in the whole animal, measuring plasma corticosteroids, ACTH and beta-endorphin. We believe that the elaboration of an inhibitor and a potentiator of CRF by the hypothalamus has important implications for the understanding of: 1) the episodic nature of ACTH and corticosteroid secretion in man, 2) the nature of the mechanisms involved in stimulating the release of ACTH and of beta-endorphin in response to noxious stimuli (stresses) in man, 3) of the changes in mood and behavior associated with response to stresses. Availability of the synthetic peptides would make it possible to examine possible extra-pituitary sites of action (e.g., nervous system). Further, availability of the synthetic peptides would pave the way to radioimmunoassay for the determination of the plasma levels of the endogenously secreted hypothalamic regulators in health and in disease.