In the last twenty years, 115 cases of Addison's disease have been observed in the Mayo Clinic. In the early days there was no specific plan of treatment, and the results were almost always uniformly bad. Prior to 1920, desultory efforts at substitution therapy were made, with occasional success. Since then every patient with Addison's disease who has gone to the Mayo Clinic has been given especial consideration from the standpoint of substitution therapy, and considerable progress has been made. Physiologic experiments have shown, with increasing clearness, that the integrity of the suprarenal cortex is essential to life and so have given impetus to the search for a form of organotherapy that would provide complete substitution. The results of recent investigations in this field justify the hope that a practical form of such treatment may soon be achieved. The natural course of the disease is usually progressively downward, with acute