The authors have previously reported that radio—labeled progesterone injected into the rat in mid—pregnancy is taken up by the myometrium at a concentration which exceeds that of the plasma. In addition, it was shown that in the pregnant rat near term this myometrial uptake of progesterone is no longer evident. Measurement of the progesterone—receptor activity in the myometrial cytoplasm, by sucrose density gradient analysis, indicated that the binding activity which is demonstrable in mid—pregnancy is markedly diminished near term. In the present experiments, the concentration of cytoplasmic progesteronereceptor sites in the myometrium has been measured, by multiple equilibrium dialysis, throughout the course of pregnancy, and the previously observed changes have been quantitatively denned. It has previously been shown by other investigators that the concentration of endogenous progesterone in rat myometrium exceeds that of the plasma in the first two—thirds of pregnancy, and that this difference in concentration disappears prior to term. In the present report it is shown that the elevation of myometrial progesterone above that of the plasma, and the subsequent disappearance of this difference, is correlated with changes in cytoplasmic progesterone—receptor site concentration. This data is interpreted as indicating that the concentration of progesterone in the myometrium of the pregnant rat is controlled, not only by plasma hormone concentration, but by changes in cytoplasmic progesterone—receptor activity. It is suggested that variation in cytoplasmic receptor activity may be a physiological mechanism for the modulation of the action of steroid hormones generally. (Endocrinology92: 394, 1973)