We have studied the control of the pituitary-adrenal axis in ovariectomized sheep following hypothalamo-pituitary disconnection (HPD) by following plasma levels of immunoreactive (ir-) products of pro-opiomelanocortin (POMC). In ovariectomized HPD ewes, gonadotropin levels were below detection limits. In contrast, levels of ir-ACTH were modestly but significantly elevated over those in matched ovariectomized control ewes, though cortisol levels were not significantly different; levels of ir-αMSH and ir-βEP (β-endorphin) were substantially and significantly raised in HPD compared with control plasma. Size exclusion HPLC showed plasma βEP/βLPH (β-lipotropin) levels to be higher in HPD than control ewes. Dexamethasone administration lowered plasma ir-ACTH but not ir-βEP; in contrast, bromocriptine lowered ir-βEP but not ir-ACTH. We interpret these data as evidence (1) that the elevated plasma levels of ir-βEP and ir-αMSH post-HPD reflect the release of the intermediate lobe from tonic inhibitory dopaminergic control and (2) that, unlike the gonadotrope, hypothalamic releasing factors are not required for the maintenance of the corticotrope, or for baseline secretion of ACTH from these cells.