From the strong affinity of the brain-cells for adrenalin which was manifested in our experiments we may strongly suspect that the Nissl substance is a volatile, extremely unstable combination of certain elements of the brain-cells and adrenalin, because the adrenals alone do not take the Nissl stain and the brain deprived of adrenalin also does not take Nissl stain. The consumption of the Nissl substance in the brain-cells is lessened or prevented by morphin, as is the output of adrenalin; and the consumption of the Nissl substance is also lessened or prevented by nitrous oxid. But morphin does not prevent the action of adrenalin injected into the circulation, hence the control of morphin over energy expenditure is exerted directly on the brain-cells. Apparently morphin and nitrous oxid both act through this interference with oxidation in the brain. We, therefore, conclude that within a certain range of acidity of the blood adrenalin can unite with the brain-cells only through the mediation of oxygen, and that the combination of adrenalin, oxygen, and certain brain-cell constituents causes the electric discharge that produces heat and motion. In this interrelation of the brain and the adrenals we have what is, perhaps, the master key to the automatic action of the body. Through the special senses environmental stimuli reach the brain and cause it to liberate energy, which in turn activates certain other organs and tissues, among which are the adrenals. The increased output of adrenalin activates the brain to still greater activity, as a result of which again the entire sympathetic nervous system is further activated, as is manifested by increased heart action, more rapid respiration, raised blood-pressure, increased output of glycogen, increased power of the muscles to metabolize glucose, etc. If this conclusion be well founded, we should find corroborative evidence in histologic changes in that great storehouse of potential energy, the liver, as a result of the application of each of the adequate stimuli which produced brain-cell and adrenal changes. The Liver Prolonged insomnia, prolonged physical exertion, infections, injections of toxins and of strychnin, rage and fear, physical injury under anesthesia, in fact, all the adequate stimuli which affected the brain and the adrenals, produced constant and identical histologic changes in the liver--the cells stained poorly, the cytoplasm was vacuolated, the nuclei were crenated, the cell membranes were irregular, the most marked changes occurring in the cells of the periphery of the lobules (Figs. 69 and 70). In prolonged insomnia the striking changes in the liver were repaired by one seance of sleep. Are the histologic changes in the liver cells due to metabolism or toxic products, or are they "work" changes incident to the conversion of latent into kinetic energy? Are the brain, adrenals, and liver interdependent? The following facts establish the answers to these queries: