The anterior pituitary adrenocorticotropic hormone (ACTH) is being used effectively for the relief of radiation sickness in those patients who are refractory to the usual methods of its treatment. These are discontinued before starting the intramuscular injections of the hormone. The results in the first 14 patients exclusively treated by ACTH are given in the hope of stimulating further investigation along this line. In order to show that the relatively small amounts of ACTH being administered to these patients are sufficient to have a real effect, white mice were exposed to lethal amounts of total body roentgen radiation and subsequently treated with ACTH in doses comparable in milligrams per gram of body weight to those used in man. The Premise and Theory The hypothesis that ACTH would alleviate radiation sickness was originally conceived on the premise that the symptoms of this condition may be caused by intoxication from tissue decomposition products resembling histamine, as indicated by relief observed in the past following administration of such anti-histaminic drugs as benadryl in some patients and adrenocortical hormone in others. If the latter relieves the nausea and vomiting (1), it seems logical to stimulate the patient's own adrenal cortex to produce more of its hormone. If roentgen irradiation is another stress which produces the “alarm reaction” of Selye (2) in patients not already debilitated by their cancer, it would seem logical to bridge them over their “stage of exhaustion,” which might be represented by radiation sickness. ACTH stimulates the normal adrenal cortex to produce glucocorticoids, including cortisone, which appear to support the replenishment of energy stores, electrolytes and water, to render the body capable of reacting adequately, physiologically, to continued stress situations such as burns, anoxia, fractures, extreme environmental temperatures or pressures, and shock (3). To these situations, I wish to add radiation sickness. ACTH should, as a rule, be preferable to cortisone for two reasons. First, ACTH would stimulate a more constant production of cortisone as compared to the peaks of concentration in the tissues which result from intermittent injections. Secondly, ACTH usually causes hypertrophy and hyperplasia of the adrenal cortex (4), with continuance of increased function for a short time after administration has been discontinued, whereas the effect of cortisone on adrenal cortical structure is just the opposite (4). The effects of ACTH depend, however, upon the sensitivity of the adrenal cortex to its stimulation (3). If the cortex is insensitive, as in Addison's disease, little benefit is gained from trying to bring it back (5). In this case, of course, cortisone is preferable to ACTH. Twenty-five years ago, while I was studying with Evans, he showed that injections of pituitary extract were followed by hypertrophy of the adrenal gland in laboratory animals (6).