1. In the ovarian egg of the frog there is a definite relation between the polar axis of the egg and its blood supply. In every case the pigmented hemisphere is more richly supplied with arterial blood than the unpigmented hemisphere. It is suggested that polarity arises in response to this external factor, viz., respiratory and nutritive relation of the egg to the parent body. It also seems probable that the localization of the pigment on the egg is in response to the greater oxygen supply over a restricted area. There is no orientation of the ovarian egg to gravity.It is pointed out that polarity in a number of other organisms arises in response to conditions external to the egg.2. It is shown that differences in susceptibility exist in different parts of the egg and embryo of the frog. These differences are evidenced in the following ways:(a) By differential death gradients,(b) By differential inhibition, and(c) By differential acclimation and recovery.3. The two modifications of the susceptibility method described in this paper, (a) and (b) above, agree in showing that:(a) Those parts of the egg where development first begins and proceeds most rapidly die soonest in lethal concentrations or intensities of external agents and are inhibited most under conditions so severe that acclimation does not occur. Both disintegration processes and inhibition are differential, paralleling the polar axis in early development and other axes that arise later. (b) All of the modifications, produced under different conditions, are essentially similar, differing not in kind but in degree. No evidence was found of "specificity," "blastolysis" or "disorganization" as effective factors in the production of any of the modifications.(c) The experimental data indicate that any type of abnormality may be produced under the influence of any inhibiting agent by controlling the concentration or intensity of action, the length of exposure and the stage in development (physiological condition) of the egg or embryo when exposed.4. Differential inhibitions, appearing under conditions that prevent acclimation, are evidenced in the following and other ways:(a) By the relatively slower division of the more active animal pole cells with the result that the cell size ratio approaches and may become equal to one.(b) By the retardation or prevention of downward movement of material from the animal hemisphere, which takes place, normally, most rapidly in the sagittal plane, but which under these conditions, is most retarded in this plane.(c) By the retardation of the dorsal lip region with the formation of V-shaped blastopores and oval yolk plugs that may be several times longer in the sagittal plane than broad.(d) By the retardation of both dorsal and lateral lips of the blastopore resulting in the formation of flat-crescent blastopores and a whole series of modifications between this and,(e) Perfect equatorial gastrulæ.(f) By the appearance of a secondary invagination apical to the original blastopore.(g) By the shifting of the blastopore so that it may come to lie at or above the equator of the egg. (Accompanies d, e, f.)(h) By the apparent obliteration of bilaterality, resulting in the formation of embryos radially symmetrical about the original polar axis.(i) In the later embryonic stages a variety of abnormal types appear most of which are later stages of c, d, e and g, above. Among them may be mentioned, microcephalic forms with eyes, nasal pits, and ventral suckers in all degrees of approximation to complete "fusion"; anencephalic forms appear, and spina bifida of all degrees are common. Most of the forms show a marked dorsal concavity and the medullary folds may remain open in the brain region or throughout their entire length.5. Since the dorsal lip region arises at the distal end of a rapidly growing region, and bears a definite spatial relation to the apical region that is experimentally controllable, it is probable that it arises by physiological isolation consequent upon the rapid growth in length, especially in the sagittal plane.6. The data presented indicate that at the beginning of development, metabolic processes are most rapid at the apical (animal) pole and decrease toward the basal (vegetative) pole.7. With advance in development a secondary region (dorsal lip) of high susceptibility appears, probably as a physiological isolation and represents a posterior "segmental" region of rapid growth similar in many respects to the posterior growing region of annelid larvæ.8. It is pointed out that the existence of gradients in metabolic rate along physiological axes in the egg and embryo make possible the great uniformity and lack of specificity shown to exist in the susceptibility relations in the frog and other organisms, and affords the basis for a rational interpretation of teratogeny, not only in the frog but also in vertebrates generally.