equilibrium between masses capable of disintegrating and products of the disintegration. It is not possible to give any detailed account as to the part taken by accumulating asphyxiation substances in the prolongation of the refractory period. Indeed, we must for the present relinquish the attempt to delimitate quantitatively the part taken by the individual constituent processes in the symptoms of depression resulting from the deficiency of oxygen. We can merely say, the individual alterations produced by the want of oxygen, that is, the restriction and retardation of the oxydative disintegration, the corresponding increase of the anoxydative decomposition and the accumulation of the products of incomplete oxydation and anoxydative breaking down have the same influence in that they decrease the strength of the response and retard the rapidity of the decomposition process. These are the general effects perceptible in the refractory period by the deficiency of oxygen. [143] _Alexander Lipschütz_: “Ermüdung und Erholung des Rückenmarks.” Zeitschr. f. allgem. Physiologie Bd. VIII, 1908. [144] _Fillié_: “Studien über die Erstickung und Erholung des Nerven in Flüssigkeiten.” Zeitschr. f. allgem. Physiologie Bd. VIII, 1908. The establishment of these facts of the dependence of the refractory period upon oxygen are of the utmost importance for the genesis of fatigue, for the state of fatigue in all aërobic organisms is invariably brought about by deficiency of oxygen. In other words: _fatigue is invariably asphyxiation_. A deficiency of organic reserve substances never occurs in fatigue before the effect of oxygen deficiency leads to complete depression, for the quantity of organic reserve substances at the disposal of the cells is greater comparatively than that of oxygen. This is shown by transfusion experiments in which the time involved before complete paralysis was brought about in the frog by the introduction of an oxygen-free saline solution was ascertained and compared with the period which elapsed before complete paralysis took place, when the same solution saturated with oxygen was used. Although the previously described experiments on the strychninized frog show clearly the relations of fatigue to the refractory period, I should, nevertheless, like to illustrate them somewhat further. The state of fatigue as it is developed in a living system by a continuous functional activity is characterized by a series of symptoms which can be best studied in the fatigue of the muscle, the nervous centers, and the peripheral nerves.