From the standpoint of the conditional method of investigation it is at once apparent that specific energy, as well as specific irritability, must be solely determined by the specific conditions existing in the particular system. It follows from this that every alteration in the conditions of the system, that is, every change of its state, likewise entails a corresponding alteration of its specific energy and its specific irritability. It is, therefore, self-evident that the alteration of the state, which is undergone by the living system in the process of excitation, brings about an alteration of its specific irritability. Likewise as the original state of the system is restored by the metabolic self-regulation after the course of an excitation, the specific irritability of the system must be reestablished. The specific irritability is, therefore, a property of the living system, which, like the metabolic equilibrium, undergoes restitution by the process of self-regulation after variation produced by a stimulus of any kind. It is scarcely necessary to repeat each time that this is only applicable within the physiological variations and for a limited period, during which the alterations in development need not be considered. These alterations of the specific irritability following an excitation and their compensation through the metabolic self-regulation will now claim our attention. That the specific irritability of a living system undergoes a diminution as the result of a stimulus of long duration has been long known through the study of fatigue. This is especially so with frequently recurring excitating stimuli. It is only within the last decade, however, that the observation has been made in a few instances that a single momentary excitation is likewise followed by such a reduction of the specific irritability. But that this is a fact of general physiological fundamental importance for the whole field of response to stimulation in the living substance has only been recognized within the last few years. [Illustration: Fig. 29. Eight series of heart contractions. The dotted lines _e_ show the moment of an artificial stimulus. The artificial stimulus is ineffective if it is applied before the height of a systole. The artificial stimulus becomes the more effective in producing an extra systole, followed by a compensatory pause, the later it is applied after the height of the systolic contraction. (After _Marey_.) ]