The effect of prenatal exposure to DES on the postnatal development of male and female genital tract function was studied. We investigated the placental transfer of [3H]- or [14C]-radiolabeled DES in pregnant mice. DES-associated radioactivity in the fetal plasma approximated maternal plasma one-half hour after iv administration of [3H]DES; [3H]-acitivity associated with DES in the fetal genital tract was about threefold higher. The decrease in reproductive capacity of female offspring from mice treated with DES during gestation was dose related; a low incidence (10% or less) of cancer of the vagina, cervix, and/or uterus was also observed in these mice. Male offspring exposed prenatally to the highest dose (100 micrograms/kg) of DES in this study also had lower reproductive capacities. Lesions in the genital tract of these mice included epididymal cysts, inflammation, cryptorchidism, and nodular masses in the seminal vesicles and/or prostate gland. Such lesions and sterility were not observed at the lower DES doses. Histologic studies with neonatal mice raise the possibility that müllerian duct tissue may represent a site for the transplacental toxicity of DES in both the male and female fetus.