The purpose of this study was to determine if large amounts of estrogenic hormones produced by the placenta could play a role in the development of the lymphoid tissue changes of pregnancy. 40 immature female rats were used. The group was divided into 4 lots of 10 animals each. The first group was castrated. The second group was castrated and given 1.5 mg of estradiol valerianate every fifth day to a total of 4.5 mg. The third group was castrated and injected with peanut oil only, the vehicle used for the estradiol. The fourth, a control group, was untreated. All animals were killed on Day 19. Spleens, genital organs, thymus glands, and mediastinal lumph nodes were removed, weighed and prepared for histologic examination. Thymus glands showed involution. The genital organs were well developed in the group receiving estradiol, but showed involution in other castrated animals. Histological examination of the thymus of animals receiving estradiol showed signs of lymphatic depletion. Spleens, lymph nodes, and adrenals appeared normal. It was concluded that estradiol, and possible other estrogenic hormones, might be of importance in the mechanisms of the immune response. This could apply to the Rh immunization of the pregnant female to her fetus.