I have described this experiment somewhat in detail as it contains facts which are the key for the comprehension of a general physiological process of paramount importance. I refer to fatigue. The refractory period and fatigue are inseparably connected, for fatigue is founded on the existence of the refractory period and is an expression of prolongation of the former, brought about by want of oxygen. This is shown at once by closer analysis. It is here necessary to differentiate somewhat more in detail the factors which bring about the _prolongation of the refractory period in deficiency of oxygen_. If we first turn our attention to the normal refractory period which occurs in a system in metabolic equilibrium of rest in direct connection with dissimilatory excitation, following a momentary stimulus, we find that reduction of irritability or, more exactly expressed, the lessening of the response is, as we have seen, determined by the time involved in the metabolic decomposition and recovery. Both these processes require time and until their completion the quantity of substance demanded for the oxydative disintegration is decreased in a given space, and every stimulus must consequently be followed by a weaker response. Our conceptions of the physical details of these processes depend essentially upon the question, if the oxydative disintegration itself in the given living system occurs in one single phase, in that the oxygen is the activator for the oxydative splitting up of the carbon chain, or if this takes place in two periods, in which the carbon chain is first anoxydatively split up into larger fragments by the stimulus, which are then seized upon by the oxygen to be split up into carbon dioxide and water. As we have seen, this question must remain for the present undecided as far as the metabolism of rest as well as the excitation produced by a single momentary stimulus is concerned. It is highly probable that a uniformity of the process for all living systems does not exist. We are, therefore, not justified in assuming that these special chemical processes resulting from single stimuli are uniform throughout the refractory period. On the contrary it is different in the case of oxygen deficiency. Here we see with increasing want of oxygen a constantly increasing duration of the refractory period, a prolongation which may be attributed to the retardation of the oxydative disintegration. It is necessary, however, that we now study more clearly these alterations brought about by the deficiency of oxygen.