Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause.