To date, no reliable method is available for predicting which patient with endometrial carcinoma will respond favorably to progestin therapy. The factors that predispose these patients to the treatment with progestogens and the mode of action of these steroid hormones are obscure. The aim of the proposed project is to ascertain whether the progesterone receptor(s), which has recently been identified and partially characterized in human endometrium, is the factor or factors which predispose endometrial carcinomas to progestin therapy. Progesterone receptor in the cytoplasmic fraction of normal, hyperplastic and neoplastic endometrial tissue will further be studied by sucrose gradient centrifugation, polyacrylamide gel electrophoresis and isoelectric focusing in polyacrylamide gel. The specific progesterone-binding capacity of each endometrial cytosol preparation will be measured by charcoal adsorption. The relative affinities of various synthetic progestogens for the progesterone receptor will be compared. The clinical course of all those patients treated with progestogens will be followed. Sufficient biochemical and clinical data will have to be collected before one could evaluate whether there is a significant correlation between the differences (quantitative and/or qualitative) in the progesterone receptor and the responsiveness of the tumor to progestin therapy. A method for predicting which new or untried progestogen will offer promise in the treatment of endometrial cancer may also be made available.