The adrenal responses to insulin-induced hypoglycemia and the rapid adrenocorticotropic hormone (ACTH) stimulation test were compared in 24 healthy volunteers, 18 of whom also underwent a rapid oral metyrapone test. The cortisol levels after hypoglycemia (18.0–30.0 μg/100 ml) were similar to and directly related to the levels after ACTH (21.0–31.0 μg/100 ml). The levels after both stimuli were independent of age, sex, height, and weight. The 11-deoxycortisol response to the metyrapone test was less than the cortisol response to hypoglycemia and metyrapone administration was associated with more unpleasant side effects. In a group of 69 control subjects, the post-ACTH cortisol levels were 15.0 to 80.0 μg/100 ml while in seven patients with Addison's disease they were <1–4.5 μg/100 ml. In 44 control subjects, the posthypoglycemia cortisol levels were 18.0 to 30.0 μg/100 ml compared with <1.0–9.0 /μg/100 ml in 22 patients with hypopituitarism. The absolute poststimulation cortisol levels provided better separation of control subjects from patients with adrenal or pituitary insufficiency than either the increment in cortisol levels or the 11-deoxycortisol response to metyrapone.