Changes in the corticotropinreleasing activity of the median eminence of rats are described following acute stress, adrenalectomy, hypophysectomy or cortisol treatment. The CRF content of the median eminence began increasing 5 days after adrenalectomy until it attained a concentration 2-2$ times that of normal animals 20 days after the removal of the adrenals. This level was subsequently maintained for at least another 30 days. The CRF content of the median eminence of rats 48 hr after hypophysectomy did not differ from normal controls. There was a rapid and marked increase in the corticotropin-releasing activity of the median eminence 1.25 min after stress in normal, adrenalectomized and hypophysectomized animals. A dose of hydrocortisone that blocks stress-induced ACTH release drastically reduced the corticotropin-releasing activity of median eminence and completely prevented the rise in CRF content of that tissue caused by stress. It is suggested that the close parallelism between the changes occurring in the median eminence and pituitary under these conditions indicates that CRF may regulate pituitary ACTH synthesis. (Endocrinology 76: 122, 1965) I T HAS BEEN demonstrated that destruction of the median eminence region of the hypothalamus results in an inability of the pituitary to respond to a stressful stimulus with increased ACTH secretion (1). Furthermore, extracts of median eminence (2, 3) or blood obtained from hypophysectomized animals (4) have been shown to possess corticotropin-releasing activity. One of the prerequisites to establishing the theory of a neurohumoral regulation of pituitary ACTH secretion would be to demonstrate that physiologic changes in the ACTH secretion of the adenohypophysis are correlated with variations in the concentration of the hypothalamic neurohumor. Although admirable studies of this type have been performed re-