Experience with intravenous ACTH and 9-alpha-fluorohydrocortisone as agents for diagnostic evaluation of the functional status of the adrenal cortex are reported. Currently, these workers administer 25 U.S.P. units of ACTH intravenously in 500 ml. of physiologic saline or 5 per cent dextrose-in-water over an 8-hour period on each of 2 successive days. Urinary 17-ketosteroids and 17-hydroxycorticoids are measured on 2 or more control days and on the 2 days of ACTH administration; blood eosinophil counts are done before and after each ACTH infusion. Prior to the 2-day ACTH test, patients who have been receiving cortisone or hydrocorisone for any reason are changed to maintenance doses of 9-alpha-fluorohydrocortisone (in the ratio of approximately 1 mg. of fluorohydrocortisone to 20 mg. of cortisone or hydrocortisone) because these small doses of fluorohydrocortisone make no appreciable contribution to the urinary 17-ketosteroids and 17-hydroxycorticoids, whereas cortisone and hydrocortisone do. Tests on 40 adult hospitalized patients who had no evidence of endocrine disease showed progressive increases in both 17-ketosteroid and 17-hydroxycorticoid output on the 2 test days. Observations are also reported on adult patients with primary adrenal insufficiency (Addison's disease), iatrogenic adrenal insufficiency, secondary adrenocortical insufficiency (hypopituitarism), and states of adrenocortical hyperfunction (bilateral hyperplasia, adrenal adenoma, adrenal carcinoma, and the adrenogenital syndrome). Each of these conditions is shown to be associated with a characteristic pattern of response. The authors conclude that standardized intravenous ACTH tests offer a practical method for investigating the nature and quantities of the adrenal secretory products, and thereby aid in the differential diagnosis of the various kinds of adrenal dysfunction.