The effect of oral clonidine challenge on cortisol secretion was evaluated in seven patients with primary degenerative dementia and in seven patients with major depression. Postclonidine cortisol levels were decreased in all depressed patients and in demented patients with hypercortisolemia at baseline. Demented patients with normal cortisol levels at baseline developed increased post-clonidine cortisol levels. These preliminary findings suggest differences in noradrenergic regulation of cortisol secretion among patients with primary degenerative dementia.