Soy-based infant formulas have been in use for >30 y. These formulas are manufactured from soy protein isolates and contain significant amounts of phytoestrogens of the isoflavone class. As determined by HPLC, the isoflavone compositions of commercially available formulas are similar qualitatively and quantitatively and are consistent with the isoflavone composition of soy protein isolates. Genistein, found predominantly in the form of glycosidic conjugates, accounts for >65% of the isoflavones in soy-based formulas. Total isoflavone concentrations of soy-based formulas prepared for infant feeding range from 32 to 47 mg/L, whereas isoflavone concentrations in human breast milk are only 5.6 +/- 4.4 microg/L (mean +/- SD, n = 9). Infants fed soy-based formulas are therefore exposed to 22-45 mg isoflavones/d (6-11 mg x kg body wt(-1) x d(-1)), whereas the intake of these phytoestrogens from human milk is negligible (<0.01 mg/d). The metabolic fate of isoflavones from soy-based infant formula is described. Plasma isoflavone concentrations reported previously for 4-mo-old infants fed soy-based formula were 654-1775 microg/L (mean: 979.7 microg/L: Lancet 1997:350;23-7), significantly higher than plasma concentrations of infants fed either cow-milk formula (mean +/- SD: 9.4 +/- 1.2 microg/L) or human breast milk (4.7 +/- 1.3 microg/L). The high steady state plasma concentration of isoflavones in infants fed soy-based formula is explained by reduced intestinal biotransformation, as evidenced by low or undetectable concentrations of equol and other metabolites, and is maintained by constant daily exposure from frequent feeding. Isoflavones circulate at concentrations that are 13,000-22,000-fold higher than plasma estradiol concentrations in early life. Exposure to these phytoestrogens early in life may have long-term health benefits for hormone-dependent diseases.