In an attempt to understand the mechanism of the antiprogestational action of estrogens during early pseudopregnancy we determined the cytosolic and nuclear concentrations of progesterone receptors in the endometrium of rabbits treated with hCG followed by various combinations of estradiol and progesterone. The progestational response of the endometrium was followed by quantitation of the uteroglobin content in the uterine lumen. In rabbits treated with hCG alone there was a clear progestational response (40% relative uteroglobin content), but only 16% of the progesterone receptors were located in the nucleus. After additional treatment with progesterone the progestational response remained high (45% relative uteroglobin content), the total cellular content of progesterone receptor increased, and 5% of the complexes were found in the nucleus. These findings suggest that a consumption of nuclear progesterone receptor is required for progestational action. Treatment of pseudopregnant rabbits with estradiol resulted in a marked increase not only of the total cellular progesterone receptor but also of the percentage of it located in the nucleus (35%). Concomitantly, the progestational response was markedly inhibited (5% relative uteroglobin content). These results confirm the relevance of nuclear consumption of progesterone receptor for progestational action, and suggest that some antiprogestational effects of estrogens may be due to their interference with the mechanism of progesterone receptor processing.