BALB/c StCrlfC3Hf/Nctr, CS7BL/6J, C57BL/6 X BALB/c F1hybrid (B6CF1), and monohybrid‐cross offspring from the breeding of B6CF1mice were examined with respect to uterine, vaginal, and thymus responses to diethylstilbestrol (DES). About 400 mice of each genetic population were used. Weanling mice were fed DES at dietary concentrations of 2.5 to 1,000 ppb (μg/kg feed) for 6 days and were killed by cervical dislocation about 20 hr after removal of the feed. C57BL/6, B6CF1, and the monohybrid‐cross offspring did not differ in the uterine‐weight response to DES, but the slope of the dose‐response line was shallower for the BALB/c than for the other strains. Dietary DES concentrations of 250 ppb or more inhibited the uterotrophic response in all populations. Vaginal cornification occurred at lower concentrations of DES in the C57BL/6 strain than in the B6CF1animals. BALB/c and monohybrid‐cross offspring were indistinguishable from each other in their vaginal response to DES and were less sensitive to DES than the other mouse populations. The use of ethanol or corn oil as the solvent for mixing DES into the diet had no apparent effect on the uterine weight or vaginal response in any of the mice. DES depressed thymus weight in a dose‐related fashion at dietary concentrations of 100 ppb and above in all genetic populations.