If we follow the course of the changes from that of the normal state of equilibrium of metabolism, wherein oxygen is sufficient to bring about complete disintegration of the molecules to the formation of carbon dioxide and water, we must assume in spite of the great explosive rapidity of this process on the basis of our chemical knowledge, that first a series of intermediate products are produced before finally the end products are formed. In this way the oxydative disintegration produced by a stimulus becomes more and more prolonged by an increasing want of oxygen. If, as I have previously suggested, the amount of energy which is liberated in a given space and time by an excitating stimulus is taken as a standard of irritability, it is apparent that the more the oxydative disintegration following a stimulus is retarded, the greater must be the decrease in irritability. The less oxygen there is at disposal and the more incomplete the oxydative breaking down, the smaller is the degree of irritability, the weaker the response and the slower the return of irritability after every stimulus. In other words, with the increasing deficiency of oxygen, the response is not merely reduced for every stimulus, but the duration of the refractory period is likewise progressively prolonged until finally with an absolute want of oxygen, constant and complete depression takes place. In the genesis of this process another factor, however, has the same effect. While with a sufficient supply of oxygen disintegration leads to the formation of carbon dioxide and water, therefore to end products, which can quickly and easily be removed by diffusion, the want of oxygen produces complex products of incomplete combustion and finally of anoxydative decomposition, such as lactic acid, fatty acids and even more complex substances in constantly increasing quantities. These products permeate the protoplasmic surfaces with great difficulty, if at all, and as they cannot subsequently be oxydatively split up, constantly accumulate. These asphyxiation substances, as they may be briefly termed, produce a depressing effect on further disintegration. This can be experimentally demonstrated.