We have recently described an experimental model for studying the hormonal modulation of growth and receptor content of human endometrial adenocarcinoma in ovariectomized athymic mice. The morphologic features of endometrial carcinomas can be maintained during serial transplantation in control animals. Further, administration of estradiol, tamoxifen citrate, and medroxyprogesterone acetate to animals with tumors containing estradiol and progesterone receptors resulted in histologic and ultrastructural changes in most foci resembling the response of normal human endometrium to these agents. No morphologic change was detected in the steroid-receptor-negative tumors of hormone-treated mice. These results demonstrate that histologic changes parallel the changes in the growth rate and hormone receptor content of tumors in this model system, and they provide support for the concept of receptor-mediated alteration in the morphologic features of endometrial adenocarcinoma.