The first fact to take into consideration is, that, as is shown in the heart, the refractory period begins at the moment of the appearance of the systolic excitation. The irritability of the heart is absent and remains so until the excitation has reached its highest point, that is, shortly before the beginning of the diastole. From this point the restitution of irritability begins, which does not reach the maximum until the end of the diastole. In other words: irritability undergoes the greatest reduction by disintegration produced by the stimulus and is restored by the metabolic self-regulation following the decomposition. This point of view enables us to interpret this state from a physical standpoint. In this discussion on the relations between irritability and the extension of excitation, I have taken the amount of energy which is produced during the time unit and space unit in a living system as the general standard for the degree of irritability, at the same time duly regarding the individual components involved. This amount of energy is determined in a given system by the quantity of substance broken down by a stimulus of a given intensity. It is, therefore, clear that during the time in which an increased disintegration produced by a stimulus takes place, the irritability in response to a second stimulus must be reduced, as during this period the second stimulus has less of necessary decomposable substances at its disposal, and at the same time there are more products of disintegration in a given space. If a living organism is the subject of consideration, to which the “all or none law” is applicable, as, for instance, the heart at the moment of the beginning of excitation, irritability is completely obliterated, as shown by the fact that the second stimulus of any strength remains without response, for during the excitation there is a complete breaking down of all the substances capable of decomposition. If, on the contrary, a system is the subject of observation, for which the “all or none law” is not valid, then irritability is merely reduced but not wholly obliterated during an excitation, and whether or not a response is obtained to the stimulus depends upon its strength. To impress the relations between the degree of irritability and the intensity of the stimulus, I have, therefore, employed the term “_relative refractory period_” in contrast to the “_absolute refractory period_,” in which irritability is obliterated even for the strongest stimuli. It is self-evident that irritability must again increase in the same degree as the restitution of the living system by metabolic self-regulation takes place, for the more molecules capable of disintegrating are restored and the more products of disintegration removed, the more molecules necessary for decomposition in the unit of space are attacked and broken down by the stimulus. All these are self-evident facts which are in accordance