The commentary by Boettger-Tong et al.(1) described the authors' experience with a commercially available, unidentified rodent diet with high estrogenic activity and the impact of this diet on the normal in vivo uterotropic response of ovariec-tomized 30-day-old Sprague-Dawley rats to exogenously administered estradiol. The purpose of this letter is to corroborate the authors' findings; to report the phytoestro-gen content of the rodent diets most fre-quently used in estrogenicity, toxicity, and carcinogenicity studies; and to recommend that careful consideration be given to the selection of a standardized open-formula diet, ideally containing minimal or nonde-tectable levels of estrogenic substances, to be used in studies that are influenced by exogenous estrogenic substances. The authors reported that the lot of feed in question contained very high amounts of two well-known phytoestrogens, genistein (210 mg/kg diet) and daidzein (140 mg/kg), which induced a near maximal uterotropic response in control rats prior to hormone treatment. Boettger-Tong et al.(1) stated that the exact source of the phytoestrogen contamination in the rodent diet remainsan open question. In our ini-tial study, we reported that soybean meal was the major source of daidzein and genistein in all six naturalingredient rodent diets assayed and that their concen-tration was directly correlated with the soybean meal content in the diets (2). Three of the six naturalingredient diets assayed contained high total daidzein and genistein concentrations. RodentLaboratory Chow# 5001 (Purina Mills, Inc., St. Louis, MO) contained 277 pg/g daidzein and 214 pg/g genistein (total of491 pg/g diet). Based on previous reports (2, 3), thisis equivalent to 4.3 ppb of calculated diethylstilbestrol (DES) activity in this diet. A diet containing 4 ppb DES induces a significant increase in the uterine weight/body weight ratio of immature CD-1 mice fed this diet for 7 days (4, 5). Mouse Chow# 5015 (Purina Mills, Inc.) contained 130 jig/g daidzein and 97 pg/g genistein (total of 227 pg/g diet); the NIH-07 diet (Zeigler Brothers, Inc., Gardners, PA)(6) contained 124, ug/g daidzein and 104 1ig/g genistein (total of228 pg/g diet) as assayed using high performance liquid chromatography coupled with mass spectrometry. This is equivalent to 2.0 ppb DES activity in both of these diets. Therefore, we agree with Boettger-Tong et al.(1) that some commercially available rodent diets contain levels of thephytoestrogens daidzeinand genistein that can alter an animal's normal response to other exogenously administered estrogens. Some laboratory rodent diets used in studies evaluating estrogenic substances, toxicity, or carcinogenicity contain levels of the phytoestrogens daidzein and genistein that could alter the results of these studies by binding to estrogen receptor sites. The estrogenicpotential of the phy-toestrogens has been clearly defined: Bickoff et al.(3) reported that 8 mg of genistein or 11 mg of daidzein in10 g of diet, consumedover 4-6 days, increased the uterine weight of immature female mice from 9.6 mg to 25 mg; Santell et al.(7) reported that 375, ug genistein per gram of diet induced a significant uterotropic response in 60-day-old ovariectomized rats. Most of the research utilizingphytoes-trogens has explored their potential health benefits for humans, but fewer studies have been conducted to determine the dietary effects of phytoestrogens on rodent estrogenic or carcinogenesis studies. The effects of dietary fat, protein, and fiber on mammary tumor incidence and tumor mass were compared in the TG. NK transgenic mouse with oncogene c-neu (erb B2). Mice were fed the AIN-76A casein-based diet (Bio-Serv …