I have never known a case of Graves' disease to be caused by success or happiness alone, or by hard physical labor unattended by psychic strain, or to be the result of energy voluntarily discharged. Some cases seem to have had their origin in overdosage with thyroid extract in too vigorous an attempt to cure a colloid goiter. One of the most striking characteristics of Graves' disease is the patient's loss of control and his increased susceptibility to stimuli, especially to trauma and to fear and to the administration of thyroid extract. It has been shown that the various causes of the discharge of nervous energy produce alterations in the nervous system and probably in the thyroid gland. This is especially true of the fear stimulus, and has been clearly demonstrated in the brains of rabbits which had been subjected to fear alone (Fig. 13). Of special interest was the effect of daily fright. In this case the brain-cells showed a distinct change, although the animal had been subjected to no fear for twenty-four hours before it was killed (Fig. 13 C. Now, a great distinction between man and the lower animals is the greater control man has acquired over his actions. This quality of control, having been phylogenetically most recently acquired, is the most vulnerable to various NOCUOUS influences. The result of a constant noci-integration may be a wearing-out of the control cells of the brain. In a typical case of Graves' disease a marked morphologic change in the brain-cells has been demonstrated (Fig. 15). As has been previously stated, the origin of many cases of Graves' disease is associated with some noci-influence. If this influence causes stimulation of both the brain and the thyroid, its excessive action may cause impairment of the brain and also hyperplasia of the thyroid. As self-control is impaired, fear obtains an ascendency and, _pari passu_, stimulates the thyroid still more actively (Fig. 16). Finally, the fear of the disease itself becomes a noci-stimulus. As the thyroid secretion causes an increase in the facility with which nervous energy is discharged, a pathologic reciprocal interaction is established between the brain and the thyroid. The effect of the constantly recurring stimulus of the noci-influence is heightened by summation. This reciprocal goading may continue until either the brain or the thyroid is destroyed. If the original noci-stimulus is withdrawn before the fear of the disease becomes too strong, and before too much injury to the brain and the thyroid has been inflicted, a spontaneous cure may result. Recovery may be greatly facilitated by complete therapeutic rest. A cure implies the return of the brain-cells to their normal state, with the reestablishment of the normal self-control and the restoration of the thyroid to its normal state, when the impulses of daily life will once more have possession of the final common path and the noci-influence will be dispossessed.