Soybean products contain high concentrations of phytoestrogens. Isoflavone is the major phytoestrogen in soy and has been shown to display estrogen-like activities. It is well known that the delivery of isoflavone components across the placenta and in milk occurs in fetuses and infants the effect of following maternal exposure to isoflavone. We examined the effect of in utero and lactational exposure to isoflavone on the development and fertility of mouse offspring over two generations (F1 and F2). Pregnant mice were given daily subcutaneous injections of isoflavone (5, 50, 100 mg/kg/day) during the gestational and lactational stages until 20 days after delivery. At postnatal day (PND) 42, the F1 pups were sacrificed, and their body masses and organs (liver, kidney, testis, epididymis, ovary and uterus) were weighed. The other F1 pups were mated with non-treated mice or F1 heterosexual mice to estimate F1 fertility and development of F2 pups. The body weights of F1 pups increased at dose of 5 mg/kg/day. The epididymis weights of F1 males increased at doses of 5 and 100 mg/kg/day. No significant differences were found in the uterus and ovary weights of F1 females in all treatments. In the F2 males, the body weights of the 50 mg/kg/day group were higher than those of the control group. The epididymis weights of the 5 and 100 mg/kg/day groups were higher than those of the control group. In the F2 females, the body weights of the 5 and 100 mg/kg/day groups and the ovary weights of the 5 and 50 mg/kg/day groups were higher than those of the control group. There was no significant difference in pregnancy rate or numbers of live or dead fetuses in any treatment for the F1 and F2 offspring. These results suggest that gestational and lactational exposure to isoflavone presumably affect the body weights and some reproductive organ weights of F1 and F2 offspring, but are not seriously harmful to potential fertility.