Vaughan has shown that the presence in the body of any alien protein causes an increased production of heat, and that there is no difference between the production of fever by foreign proteins and by infections. Before the day of the hypodermic needle and of experimental medicine, the foreign proteins found in the body outside the alimentary tract were brought in by invading microorganisms. Such organisms interfered with and destroyed the host. The body, therefore, was forced to evolve a means of protection against these hostile organisms. The increased metabolism and fever in infection might operate as a protection in two ways--the increased fever, by interfering with bacterial growth, and the increased metabolism, by breaking up the bacteria. Bacteriologists have taught us that bacteria grow best at the normal temperature of the body, hence fever must interfere with bacterial growth. With each rise of one degree centigrade the chemical activity of the body is increased 10 per cent. In acute infections there is aversion to food and frequently there is vomiting. In fever, then, we have diminished intake of energy, but an increased output of energy--hence the available potential energy in the body is rapidly consumed. This may be an adaptation for the purpose of breaking up the foreign protein molecules composing the bacteria. Thus the body may be purified by a chemical combustion so furious that frequently the host itself is destroyed. The problems of immunity are not considered here. As to the mechanism which produces fever, we postulate that it is the same mechanism as that which produces muscular activity. Muscular activity is produced by the conversion of latent energy into motion, and fever is produced largely in the muscles by the conversion of latent energy into heat. We should, therefore, find similar changes in the brain, the adrenals, the thyroid, and the liver, whatever may be the purpose of the conversion of energy-- whether for running, for fighting, for the expression of emotion, or for combating infection. We shall first present experimental and clinical evidence which tends to show what part is played by the brain in the production of both muscular and febrile action, and later we shall discuss the parts played by the adrenals, the thyroid, and the liver. Histologic Changes in the Brain-cells in Relation to the Maintenance of Consciousness and to the Production of the Emotions, Muscular Activity, and Fever