Studies on the cholecystokinin-like immunoreactivity (CCK-IR), of the medial basal hypothalamus (MBH) were performed in rats. In immunohistochemical studies, a dense CCK-IR-positive staining was found in the external layer of the median eminence adjacent to portal capillaries. Either high potassium (56 mM) or veratridine (1–50 µg/ml) stimulated the release of CCK-IR from MBH incubated in vitro. This increase in CCK-IR release depended on the presence of calcium. In vivo, the content of CCK-IR in the MBH was reduced after bilateral adrenalectomy and this effect of adrenalectomy was reversed by dexamethasone treatment. The content of CCK-IR in the neurointermediate lobe of the pituitary gland was not changed under these conditions. These results raise the possibility that after activation of the hypothalamo-pituitary-adrenal axis cholecystokinin may be secreted from nerve terminals in the external layer of the median eminence into the hypophyseal portal blood.