Genistein, the principal soy isoflavone, was previously shown to induce uterine adenocarcinomas by 18 months of age in female CD-1 mice following administration by subcutaneous injections on postnatal days 1-5. A serum pharmacokinetic analysis of genistein in male and female mice treated identically showed that: maximal concentrations of total (conjugated+aglycone) genistein in females (6.8+/-1.4 microM) and males (3.8+/-1.1 microM, mean+/-SD) were comparable to those previously reported from dietary exposures in adult rats or in human infants consuming soy formulas; the average fraction present as active aglycone (31%) was similar to those in fetal and neonatal rats from placental and lactational exposures; and elimination half-times were longer than those in rats (three- to seven-fold) and adult humans (two- to three-fold). These results are consistent with a diminished capacity for enzymatic conjugation of genistein, based on the ontogeny, as an important determinant of estrogenicity in neonatal mice.