Irreversible proliferation and cornification of the mouse vaginal epithelium were induced by 10 daily injections of 20 pg estradioLl7p starting on the day of birth. Development of the irreversible vaginal epithelium during the period of estrogen injections in early postnatal life was observed under light and electron microscopes, Small electron-dense cells (A-cells) in clusters were present in the columnar vaginal epithelium of newborn mice. A-cells were proliferated by 2 daily estrogen injections. At the sites of A-cell clumps, large electron-dense cells (B-cells) characterized by long winding cytoplasmic processes appeared in mice given 3 daily injections, forming nodules which then fused together to form a layer under the columnar epithelium after 4 daily injections. In mice given 7 daily injections, the primary epithelium was shed by the superficial cornification of the newly formed layer. The Bcell membrane bore fewer desmosomes than in !he basal and intermediary cells of the vaginal epithelium of ovariectomized 'normal' adult mice after 5 daily injections of 100 pg estradioL17P. Hyperplastic epithelial downgrowths in old ovariectomized mice given neonatal estrogen injections contained another type of cells with reduced density which formed much fewer processes and only a few desmosomes (C-cells).Five to ten daily injections of estrogen starting on the day of birth cause proliferation and cornification of the mouse vaginal epithelium, which persist without further administration of estrogen (TAKASUGI, 1963; KIMURA et al., 1967;MORI, 1967;KOHRMAN and GREENBERG, 1968; for review, see TAKASUGI et ul., 1970). These changes in the vaginal epithelium are irreversible, frequently resulting in cancerous or precancerous lesions in neonatally estrogenized mice of more than 6 months of age (DUNN and GREEN, 1963; TAKASUGI and BERN, 1964; KIMURA and NANDI, 1967; MORI, 1969).Recently, TAKASUCI (1 97 1) has demonstrated that clumps of small-sized cells