Female mice from three inbred strains (BALB/cCrgl, C3H/Crgl, and C57BL/Crgl) and one noninbred stock [RU:NCS (RU)] were treated perinatally with estradiol benzoate (EB), diethylstilbestrol (DES), or sesame oil and were killed on postnatal days 30--36. A combined prenatal and neonatal regime of EB injections resulted in the abnormal presence of columnar epithelium in the vaginal fornices of some of the mice from each strain or stock. The same epithelial abnormalities were also present in the vaginal fornices of 30-day-old RU:NCS(RU) mice that had been treated only neonatally with EB or DES. The incidence of these lesions was 40--67% in the mice treated prenatally and neonatally with EB, 68% in the neonatal EB treatment group, and 100% in the neonatal DES treatment group. The columnar cells were arranged either as single layers in areas of the fornical lining epithelium or as glandlike or cystic structures in the subepithelial stroma. No cells of this type were detected in any of the samples from sesame oil-inoculated control mice. No comparable epithelial lesions were detected in the common cervical canal of the perinatally estrogen-treated animals, but this treatment consistently resulted in gross structural abnormalities at this site.