The relationship between vitamin A deficiency and estrogen as etiological agents of uterine stratified squamous metaplasia (keratinizing metaplasia) was studied using the rat. This is the initial attempt to correlate plasma levels of vitamin A with the uterine lesions. From the results the following conclusions can be drawn. Uterine metaplastic lesions which develop in estrogen-treated rats are not a result of generalized hypovitaminosis A, since plasma levels of vitamin A are not altered in animals treated with estrogen. Estrogen per se can cause uterine keratinizing metaplasia. The histopathologic lesions occur more frequently in vitamin Adeficient estrogenized rats having decreased plasma vitamin A levels as compared to rats with normal vitamin A intake. The two insults are complementary in producing epithelial metaplasia of the endometrium of the rat.