Finally, the question remains, is the original state, as it existed before the influence of the stimulus, really completely recovered by metabolic self-regulation, or does even individual excitation of brief duration produce a continued change in the protoplasm? It is quite impossible to prove that such an effect follows the momentarily acting single stimulus, if stimulation has not exceeded the physiological limits of intensity. Should it exist, it must be imperceptible. Nevertheless, it ought to be possible by frequently repeated application of the stimulus to increase this which is imperceptible to an extent in which it is perceptible. This is, indeed, the case and is manifested as we have already seen in the increase of the volume of living substance by frequently recurring functional excitation. We can, therefore, assume with great probability that even the momentarily acting individual stimulus produces, although not perceptible _per se_, lasting effect in the cell. The functional excitation must be followed secondarily by an increase of the assimilative phase of the entire cytoplastic metabolism. Otherwise the taking place of the increase of volume of the living system following frequent excitation of the functional constituent members of metabolism, is unintelligible. But how are we to interpret these secondary results from a physical standpoint? First of all, it must be stated that we do not know of such hypertrophy following activity in unicellular organisms, but only in the tissues and organs of multi-cellular forms, in muscles, nerve cells, glands, etc. In the cell community of the vertebrates, however, the studies on the relations between activity and the blood supply of the particular tissue or organ furnish a physical interpretation for the existence of the functional hypertrophy. The active portions show a dilation of the blood vessels, therefore an increased supply of blood and consequently an increase in the circulation of lymph. In other words: the supply of nourishment to the individual cell and the removal of the metabolic products in a unit of time is increased. The preceding discussion of the dependence of the conditions of equilibrium upon the quantitative relations of the reacting substances makes it clear that under these conditions a metabolic equilibrium on a higher quantitative level must occur; that is, the living substance must increase in amount just as in the inanimate example the absolute amount of the æthylacetat increases if more alcohol and acetic acid are introduced to an equal degree. Some time ago[76] I expressed the opinion that the increase of the blood supply in a functionally active organ must be based on a physical self-regulation, which takes place as a result of the fact that metabolic products of the tissue cells influence the cells of the vessel walls in that part, so that the vessels dilate and more lymph is formed. In the meantime this has been proved to be indeed the case.