Synthetic ovine corticotropin releasing factor (o-CRF) was administered as an intravenous bolus (100 micrograms) to eight patients suffering from a major depressive disorder, endogenous subtype. All patients showed inadequately suppressed cortisol levels after 1 mg dexamethasone. After clinical remission and normalized dexamethasone responses, these patients were reinvestigated with o-CRF stimulation. The mean adrenocorticotropic hormone (ACTH) release from the pituitary corticotroph cells was indiscriminate at both test sessions. Cortisol and corticosterone output after o-CRF tended to be higher during depression than after recovery. The o-CRF-induced increments observed with corticosterone were more marked in comparison with cortisol. Within the limitations of the current protocol, our preliminary data lend support to the view that an increased pituitary ACTH reserve or adrenocortical steroid reserve is not likely to be responsible for the defective pituitary-adrenal regulation in some dexamethasone-resistant depressives.