ABSTRACT A patient with Addison's disease remained hyperpigmented despite customary replacement therapy with glucocorticoid and mineralocorticoid. Plasma ACTH and MSH concentrations were found to be elevated, but could be suppressed by large doses of glucocorticoid, indicating a pituitary origin for these hormones. When graded doses of cortisol were administered, the patient demonstrated inappropriately high plasma levels of ACTH and MSH for each quantity of cortisol given, and the normal diurnal rhythm in plasma ACTH and MSH concentrations was lacking. These aberrations in regulation of ACTH and MSH are consistent with a diagnosis of Cushing's disease superimposed upon pre-existing Addison's disease.