A major source of exogenous estrogenic substances, which may affect laboratory animals, comes from the diet. To test the possibility that commercially available rodent diets may significantly influence uterine weights and uterine:body weight (U:BW) ratios, estrogen bioassays were performed using female CD-1 mice weaned at 15 days of age and assigned randomly to a variety of commercial test diets or to a control diet (Purina #5002) containing 0 or 6 ppb added diethylstilbestrol (DES) for comparison. Mice were housed five per cage and given deionized water and feed ad libitum. Uterine:BW ratios from 15 mice per diet were determined after 3, 5 and 7 days of feeding. Mice fed The American Institute of Nutrition purified diet (AIN-76A) or the Purina #5015 natural ingredient breeder diet had significantly (P less than 0.05) increased U:BW ratios at 3, 5 and 7 days post weaning when compared to the control diet without added DES. This increase in U:BW ratios was similar to the U:BW ratios observed in a natural ingredient maintenance diet (Purina #5002), containing 6 ppb of DES. These results show that significant differences exist in the level of substances which can cause increase in uterine weight in some commercial diets. The diet may be important when performing or comparing certain types of studies, especially those relating to estrogenic substances. A standardized diet with minimal estrogenic activity may be desirable for such studies. It is unclear from the present studies what substances might be responsible for the uterine growth promoting activity in the diets examined.