The site of inhibitory action of glucocorticoids on the hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was studied using a combination of glucocorticoid implantation and immunohistochemistry. Adrenalectomy increased the number and the staining intensity of the neurons containing CRF-like immunoreactivity in the anterior and medial parvicellular subdivisions of the paraventricular nucleus (PVN) and induced the appearance of AVP-like immunoreactivity in the same cell population. These effects of adrenalectomy were inhibited only by those dexamethasone implants which were placed close to the PVN. Unilateral implantation of dexamethasone into the PVN inhibited the adrenalectomy-induced changes in CRF and AVP immunostaining only on the implanted side. Dexamethasone implants placed into the hippocampus decreased the effect of adrenalectomy in the PVN while similar implants into the amygdala and cerebral cortex were ineffective. These results suggest that the primary site of glucocorticoid feedback inhibition on the hypothalamic secretagogues of adrenocorticotropin is the PVN.