Soy-based infant formula (SBIF) can be a substantial source of soy isoflavones during early life. Because soy isoflavones have the capacity to mimic endogenous estrogen and thereby exert hormone-like effects, there is concern regarding reproductive health. The objectives were to determine if neonatal exposure to soy isoflavones altered reproductive health in females and, if so, whether such effects are transferred to subsequent generations. CD-1 mice were bred and F1 mouse offspring were cross-fostered at birth and randomized to 1 of 4 treatments: 7 mg soy isoflavones · kg body weight(-1) · d(-1) or corn oil from postnatal d (PND) 1 to 10 or from PND 1 to 21 (n = 8-13 females/group). Mice were subsequently bred to control males on PND 56 to obtain F2 females (n = 10-15/group). F1 mice that received isoflavones had ~15% greater body weight during wk 4-8 and markedly reduced fertility with a 55-60% success rate. Reduced fertility was associated with abnormal estrus cycles, fewer corpora lutea in ovaries, and increased incidence of hyperplasia and atypia in the uteri. Offspring (F2 mice) of isoflavone-treated F1 mice had ~15% higher body weight by wk 8 through 16 of age than controls and fertility was normal. In summary, early exposure to soy isoflavones resulting in serum isoflavone concentrations similar to human infants fed SBIF reduced fertility in F1 but not F2 mice and increased body weight in both generations of female offspring. Extrapolation of these findings to the human scenario are complex but can provide guidance for more fully understanding the implications for infants consuming SBIF.