|Testosterone, the male androgen responsible for maintaining the male phenotype, is produced by testicular Leydig cells. Leydig cells express estrogen receptors and are therefore regulated by estrogen. Soybeans predominantly contain the isoflavones genistin and daidzin which are hydrolyzed in the gastrointestinal tract to genistein and daidzein. Although both genistein and daidzein possess estrogenic properties, it is unclear whether the controversial effects of soy-based infant formulas on testicular function are due to the independent actions of genistein or daidzein or result from both agents acting together. In the present study, lactational exposures to both genistein and daidzein together induced Leydig cell proliferation and decreased Leydig cell T production in 22- and 35-day-old Long-Evans male rats. In addition, lactational exposure to both genistein and daidzein reduced serum testosterone concentrations in male rats 22 days of age. Decreased androgen production persisted into adulthood, during which estrogen receptor 1 protein levels were increased and expression of many steroidogenic enzymes were impaired as a consequence to lactational exposures to both genistein and daidzein. Also, lactational exposure to genistein and daidzein decreased Sertoli cell product MIS and increased MIS type II receptor expressions in 22-day-old male rats. These observations indicate that genistein and daidzein behave in a dose-additive manner, and exposures to both isoflavones during the lactational period may also interfere with Leydig-Sertoli cell interaction, with an implication for overall testis function.