The metyrapone (Metopiron) test (MT), a useful and reliable procedure for assessing hypothalamic-pituitary-adrenal (HPA) axis function, was applied to manic patients and healthy subjects. Three out of 11 patients had high normal responses to metyrapone, as observed in patients with Cushing's disease. One patient exhibited a subnormal response to metyrapone, as occurs in patients with adrenal insufficiency. No such abnormalities were detected in 11 matched healthy control subjects. These preliminary results suggest that the HPA axis activity patterns in mania may be more complex than previously reported.