The unraveling of our knowledge of the functions of the adrenal gland constitutes one exciting development of modern medicine and biochemistry. We owe these advances to the felicitous cooperative efforts of the clinical investigator and the biochemist. Three centuries elapsed between the first recorded anatomical descrip tion of the adrenals and the demonstration by Dr. Addison in the mid-nineteenth century of the fatal results of the destruction of these glands by disease. It became evident from this observation that the adrenals secreted a "factor" or "factors" essential to life. It took approximately 90 years to isolate this elusive vital factor - cortisone - from beef adrenal cortices, independently by both Reichstein and his co-workers in Basle and Kendall and his group in the United States and another 10-15 years before it became more generally available for experimental and clinical use. It is perhaps difficult to believe that as recently as 35-40 years ago, before cortisone and cortisol were clinically available, the surgical removal of a benign adrenal cortical tumor in patients with Cushing's syndrome was associated with a prohibitive postoperative mortality rate. Within 12-36 h after operation, most of such patients developed an intractable state of shock, which was not manifested by significant electrolyte abnormalities or hypoglycemia and was unresponsive to the usual treatment for shock plus the generous use of salt-retaining hormone.