A study was made of the endometria of 16 patients with gonadal dysgenesis who had been give cyclic replacement treatment with conjugated estrogens for 2 to 10 years, and of 9 other patients who had received medroxyprogesterone in addition to the conjugated estrogens for 2 to 5 years. Seven of the former group showed varying degrees of endometrial hyperplasia, and in all of these cases the duration of estrogen therapy had exceeded 5 years. At the time of the study no cases had developed frank adenocarcinoma. Only 1 of the 9 patients who had been given medroxyprogesterone in addition to the conjugated estrogens demonstrated evidence of hyperplastic change. Progesterone may afford some protection against the development of endometrial hyperplastic activity, but its potential role in protecting against neoplasia remains to be determined. This study supports the view that estrogen replacement therapy in gonadal dysgenesis carries the risk of endometrial hyperplasia and neoplasia. Possible methods of decreasing this hazard are discussed.