Administration of synthetic ovine corticotropin-releasing factor led to rapid, parallel increases in adrenocorticotropin and alpha-melanocyte-stimulating hormone concentrations in rat plasma. Prior treatment with dexamethasone almost completely blocked the adrenocorticotropin response but not the increase in melanocyte-stimulating hormone. These data demonstrate that corticotropin-releasing factor is a potent stimulator not only of adrenocorticotropin secretion from the corticotrophs of the anterior pituitary gland but also of peptide secretion from the intermediate lobe. Such data suggest that melanocyte-stimulating hormone and beta-endorphin play a role in the physiological response to stress.