Background: Genistein and daidzein are estrogenic isoflavones found in soybeans. Circulating isoflavones in infants fed soy formula are at serum concentrations 3 or 4 orders of magnitude higher than estradiol, so that even if they are weak and readily excreted, there is so much that they should be active. Clinical trial data show increases in cholesterol synthesis consistent with an estrogen effect in infants fed soy formula vs. human milk or cow milk formula, and lowered response to polio vaccination, which might or might not be an estrogen effect. Anatomic, sonographic, and other biochemical evidence of estrogen exposure has not been looked for in infants fed soy. Plausible effects include 1) anatomic expression of estrogen activity: breast buds, labial size, vulval anatomy, scrotal rugae, and, by ultrasound, small ovarian cysts and possibly prostate volume and 2) biochemical evidence of activity: decrease in gonadotropins, decrease in estrone/estradiol synthesis. Whether such widely used products do or do not have clinically detectable estrogenic activity in infants, the group with the highest exposure per kilo, is important clinically and from a public health viewpoint. Aims: We are beginning a clinical trial in which we randomly assign and then observe infants on soy formula with and without soy estrogens to see if their exposure to soy estrogen prolongs anatomical and biochemical evidence of estrogen exposure and response. The time course of these findings in infants is not well characterized, and detailed planning of the trial will require a substantial amount of pilot work.Plausible effects include 1) anatomic expression of estrogen activity: breast buds, labial size, vulval anatomy, scrotal rugae, and, by ultrasound, small ovarian cysts and possibly prostate volume and 2) biochemical evidence of activity: decrease in gonadotropins, decrease in estrone/estradiol synthesis. Pilot studies will begin in Summer, 2003 Accomplishments: This project is in the planning stage. We have reviewed the literature, contructed a preliminary protocol, completed external review, and had a planning meeting with outside experts. Clinical field site awards were made in summer, 2002, and planning meetings hels starting in July, 2002. Phytoestrogen analyses will be done by FDA and CDC. Hormone analysis will be done by NICHD, and data handling and analysis will be directed at NIEHS.