i. Degenerations of embryonic cells have either been reported as such or have been misinterpreted by various authors as ‘mitotic metabolites’ or blood cells.

2. There is ample support for the morphological identification of dying cells from the following considerations: the degeneration ‘granules’ are initially Feulgen-positive and have thus originated from nuclear constituents; the stages of cell deaths seen in normal embryos are identical with those produced experimentally and with those observed directly in tissue cultures; degenerating cells react in the same manner to supravital stains in vivo and in vitro.

3. The process of degeneration varies with the degree of specialization of the cell, with its functional state (e.g. mitosis), with the type of animal and under experimental conditions with the causative agents.

4. Cell death may take from less than 1 hr. to about 7 hr. when only a small proportion of a living tissue dies, but may be prolonged to days when numerous cells die simultaneously and their resorption is delayed.

5. Degenerations have been found during the normal development in embryos of all vertebrate animals examined. The occurrence of necrosis in embryos of pure genetical lines is excluded from this article.

6. The incidence of embryonic cell deaths according to site, tissue, developmental stage or process and type of animal is summarized in Table 1.

7. While some degenerations have no obvious function in embryonic development, others seem to play a significant role in embryonic processes, e.g. the morphogenesis and histogenesis of tissues and organs, and the representation and regression of phylogenetic steps (Table 2).

8. Morphogenetic degenerations precede changes in the form of epithelial organs, e.g. during the invagination of the optic cup, the formation of the crystalline lens, the olfactory pit, the neural tube, etc. They bring about the separation of rudiments such as that of the neural tube and the lens from the ectoderm. They reduce the excessive thickening of uniting edges such as those of the body wall and of the mandibles. They are involved in the production of lumina in the solid rudiments of glands and the intestinal tract. In the mesenchyme they precede and make possible the influx of specialized tissue such as the sternal plates or the ingrowth of myogenic tissue in the mandible.

9. Histiogenetic degenerations are related to the differentiation of tissues and organs. The differentiation of the three cell layers of the frog tadpole retina, for instance, is accompanied by three waves of degeneration. Similar cell deaths of early neuroblasts are found in the spinal ganglia outside the limb regions. In amphibia a partial sarcolysis during metamorphosis provides a blastema for the permanent musculature. Sex differentiation of the individual involves the partial degeneration of the Mullerian or Wolffian ducts. Cell deaths also occur in relation to fibre formation and to the appearance of bone and cartilage matrix. Their role in these and in evocatory processes needs further elucidation. Whether cell deaths in the central nervous system and the sense organs at the time of vascularization and neurotization are related to these phenomena remains to be further investigated.

10. Phylogenetic cell deaths are of two types: those which represent a vestigial organ such as the paraphysis or the second muscle stage in higher vertebrates, and those concerned with the regression of larval structures such as the conjunctival papilla, parts of the ganglia of branchial nerves, of the pro- and mesonephros. Some of these larval organs have a function in embryonic development, viz. the apical ridge on the limb buds.

11. The causation of the distinctly localized morphogenetic degenerations is obscure. Vascular or nutritional disturbances are unlikely to be responsible for these cell deaths which precede changes in form and appear in the same localizations and amounts in the vascularized tissue of the intact embryo and after explantation in tissue cultures.

. Most of the histiogenetic and phylogenetic cell deaths, as well as some of the not strictly localized morphogenetic degenerations, may be due to the fading out of stimuli for their proliferation or for the completion of their differentiation. If such cells fail to divide, they age and die on reaching the end of their normal life span. This conception assumes that stimuli for the formation of embryonic tissues and organs act for limited periods only and extend over a field of cells. Some of these cells respond fully to stimulation, while others are late to react or do so only partially or receive only a fraction of the whole stimulus. The partial differentiation of cells unfits them for division, for dedifferentiation and redifferentiation in another direction.

12. The localized morphogenetic degenerations are correlated with the incidence and orientation of mitosis and of cell movements, and changes in the form of embryonic organs are brought about by the integration of these three cellular activities. Cell deaths are abundant wherever the regular arrangement and close packing of cells prevent free cell movements; they are rare or absent when, as, for instance, in the tadpole eye, a loose arrangement of cells and a decrease in cell volume (by resorption of yolk) allow of free cell movements.

14. Cell degeneration in vertebrate ontogeny is an important mechanism of integration of cells into tissues and organs by helping to shape the form of organs, by the removal of superfluous cells or by the preparation of a dedifferentiated blastema in histio- and phylogenesis.