Ziegler first advocated the view, in the first edition of his _Lehrbuch_, that hypertrophy is due to a lessening of the resistance to growth. He thinks that while hyperæmia and transudation may support the new growth, they are never the only cause of the formation of new tissue. While Virchow’s view that any injury to the body or to an organ excites proliferation finds support in the work of Stricker and Grawitz, yet the view has been combated by Cohnheim and by Weigert, and is no longer held by many pathologists. Ziegler points out that as a result of his own work, and that of his students, traumatic and chemical lesions are not followed at once by new growth of the tissue, but by degeneration of the tissue, and by changes in the circulation that lead to exudations. The new growth begins, at the earliest, eight hours after the operation, and generally only after twenty-four hours. Also after mechanical, chemical, or thermal injuries, a long interval elapses before phenomena of growth begin. The injury itself does not appear to produce the growth, but brings about those conditions that lead to cell-multiplication. Ziegler discusses what is meant by the idea of a lessening of the resistance to growth. He himself does not mean by this that hypertrophy depends on changes in the physical conditions, because it is known that living phenomena are the outcome of chemical processes and it is, therefore, _à priori_ probable that the effect is brought about by chemical substances in the fluids of the tissues. These substances affect functional actions, and may even bring about regenerative changes. This action of chemical substances on the formative activity of the cell is theoretically possible in either of two ways; first, chemical substances of definite concentration are set free, or, second, chemical substances are present in the normal condition that prevent proliferation, but if their influence should be counteracted by other substances the conditions become favorable to growth. It is known in the case of certain unicellular organisms, that derive their nourishment from the surrounding medium, that their increase in number may be retarded by the presence of certain chemical substances. It is also known that certain organisms may themselves produce chemical substances that prevent their own multiplication. It is, therefore, at least conceivable that after a part has been injured a new substance may be produced that acts upon and destroys in the organ itself the substances there present that have prevented its further growth. The other interpretation is that in the breaking down of the tissue of the organ a substance is produced that excites the cells to proliferation.