Neonatal female BALB/cCrgl mice (mammary tumor virus unexpressed) were given a daily injection of estradiol and/or progesterone for 5 days, beginning within 36 hr after birth. About one-half of each group was ovariectomized when 40 days old, and all mice were killed when between 18.5 and 26 months of age. Neonatal progesterone leads to ovary-dependent persistent vaginal cornification and hyperplasia. In addition, 16 of the 24 progesterone-treated mice had genital tract lesions, and 4 of these showed predominantly glandular features. No such lesions were observed in either oil-treated or untreated mice. Lesions were also observed in both intact and ovariectomized mice treated with estrogen-progesterone combinations, but most of the lesions were not as severe as those seen in mice treated neonatally with progesterone alone, and they were predominantly squamous in appearance. Although mammary tumors were not observed in either the control or the neonatally steroid-treated intact mice, many in the latter groups possessed hyperplastic alveolar-like mammary nodules and other abnormalities.