: Epidemiological studies have associated soy diets with reduced risk of breast and some other cancers, and oxidative cellular damage may contribute to the development of these and other diseases. We tested the effect of a soymilk supplement rich in isoflavones on a measure of cellular lipid peroxidation in a controlled feeding study. Eight premenopausal women consumed a constant diet that included soymilk containing 113-207 mg/day total isoflavones and 4 mo later a constant soy diet low (<5 mg/day) in isoflavones, both for a complete menstrual cycle. The average daily urinary excretions of daidzein and genistein were 24.6 ± 10.1 and 9.2 ± 6.1 mg/day, respectively, during the high-isoflavone soy diet and were below the detection limit during the low-isoflavone diet. F2 isoprostane 8-iso-PGF-2α excretion varied widely within and between subjects, and the group mean was not significantly different during the high- and low-isoflavone soy diet (7.67 ± 1.13 and 8.65 ± 1.18 nmol/12 h, mean ± SD, respectively). However, individual changes in 8-iso-PGF-2α between the two soymilk drinks were significantly associated with age (r = ―0.87; P = 0.006) and several measures of isoflavone exposure, namely, daidzein dose (r = 0.81; P = 0.015), combined daidzein and genistein dose (r = 0.77; P = 0.03), and total urinary excretion of isoflavones (daidzein, genistein, and equol) (r = 0.71; P = 0.05). The findings suggest that soy isoflavones may reduce lipid peroxidation in an age-dependent manner, with greater effects in older women, and with lower doses of isoflavones.