In brief, the agencies that in our brain-cell studies were found to cause hyperchromatism followed by chromatolysis gave positive results in the Cannon test for adrenalin (Fig. 62). The one agent which was found to protect the brain against changes in the Nissl substance-- morphin--gave a negative result in the Cannon test for adrenalin. After excision of the adrenals, or after division of their nerve supply, all Cannon tests for adrenalin were negative. Histologic Study of the Adrenals.--Histologic studies of the adrenals after the application of the adequate stimuli which gave positive results to the Cannon test for adrenalin are now in progress, and thus far the histologic studies corroborate the functional tests. In hibernating woodchucks, the cells of the adrenal cortex were found to be vacuolated and shrunken. In one hundred hours of insomnia, in surgical shock, in strong fear, in exhaustion from fighting, after peptone injections, in acute infections, the adrenals undergo histologic changes characteristic of exhaustion (Figs. 66 to 67). We have shown that brain and adrenal activity go hand in hand, that is, that the adrenal secretion activates the brain, and that the brain activates the adrenals. The fundamental question which now arises is this: Are the brain and the adrenals interdependent? A positive answer may be given to this question, for the evidence of the dependence of the brain upon the adrenals is as clear as is the evidence of the dependence of the adrenals upon the brain. (1) After excision of the adrenals, the brain-cells undergo continuous histologic and functional deterioration until death. During this time the brain progressively loses its power to respond to stimuli and there is also a progressive loss of muscular power and a diminution of body temperature. (2) {illust. caption = FIG. 66.In our crossed circulation experiments we found that adrenalin alone could cause increased brain activity, while histologically we know that adrenalin alone causes an increase of the Nissl substance. An animal, both of whose adrenals had been excised, showed no hyperchromatism in the brain-cells after the injection of strychnin, toxins, foreign proteins, etc. (3) When the adrenal nerve supply is divided (Cannon-Elliott), then there is no increased adrenal activity in response to adequate stimuli. From these studies we are forced to conclude not only that the brain and adrenals are interdependent, but that the brain is actually more dependent upon the adrenals than the adrenals upon the brain, since the brain deteriorates progressively to death without the adrenals, while the adrenal whose connection with the brain has been broken by the division of its nerve supply will still produce sufficient adrenalin to support life.