The neonatal mouse model has proven to be an effective system to examine long-term reproductive tract abnormalities resulting from early exposure to estrogens. Newborn C57BL/Crgl mice received 8 x 10(-2) micrograms diethylstilbestrol (DES) or 100 micrograms coumestrol (a plant estrogen) in 0.005 mL dimethyl sulfoxide (DMSO) or DMSO alone or received no treatment for the first 5 days of life. Half of the animals were ovariectomized at 40 days of age. Vaginal lavages were examined for 15 consecutive days before termination at 13 months of age, at which time genital tracts and mammary glands were removed for histological examination. Diethylstilbestrol- and coumestrol-treated animals exhibited ovary-independent persistent vaginal cornification as well as cervico-vaginal pegs and downgrowths, uterine squamous metaplasia, and an enhancement of age-related changes in the ovary including hemorrhagic follicles. In general, neonatal exposure to the naturally occurring plant estrogen, coumestrol, has long-term effects similar to those seen following exposure to natural and synthetic estrogens.