This study defines the pituitary B-endorphin (BE) secretory response to a low dosage (0.3 ug/kg) of human corticotropin releasing hormone (CRH) in depressed patients and normal controls pretreated with metyrapone. We find no difference in the B-endorphin response to CRH in depressed subjects without evidence of HPA overactivity, compared with controls. This finding is contrasted with other data demonstrating a blunted B-endorphin response to CRH in depressives. The influence of metyrapone pretreatment on the pituitary B-endorphin response to CRH through a mechanism that minimizes the impact of cortisol negative feedback is discussed. Future studies which include low dose CRH infusion both in the presence and in the absence of metyrapone pretreatment will help investigate alterations in the regulation of pituitary B-endorphin secretion in depression including the possibility of increased pituitary sensitivity to the negative fast feedback of cortisol.