Preliminary evidence has indicated that the number of nuclear bodies in uterine luminal epithelial cells of the immature rat may be related to the duration of nuclear retention of the estrogen receptor complex (Clark et al., 1978). To test this hypothesis, an ultrastructural analysis of nuclear and cytoplasmic differentiation was performed at 4, 12, 24, 48, and 72 hr after a single injection of estradiol or nafoxidine (synthetic estrogen agonist/antagonist) into 21 day female rats. Variations in nuclear and cytoplasmic differentiation and in the frequency of occurrence of nuclear bodies (simple and complex) were determined and compared with established biochemical changes in the concentration of nuclear estrogen receptor and RNA polymerase activity (Clark et al., 1978). Following nafoxidine there is sustained elevation of the nuclear concentration of the estrogen receptor as well as RNA polymerase I and II activities over the entire 72-hr period. From 4 to 72 hr the height of the luminal epithelial cell as well as the frequency of nuclear bodies increase at linear rates. Through steady expansion of the cytoplasmic membrane system (RER) and Golgi) the relatively undifferentiated epithelial cells of the control uterus are converted progressively into ones equipped for protein secretion. At 72 hr the effects of an estradiol implant resemble closely those observed after a single injection of nafoxidine; these include sustained nuclear receptor occupancy, elevated RNA polymerase activity, epithelial hypertrophy, and high frequency of nuclear bodies. However, after a single injection of estradiol, the luminal epithelial cells become slightly but significantly taller than the control cells and remain close to this size from 24 to 72 hr.; the frequency of nuclear bodies decreases linearly from 4 to 72 hr to fall below the control level. In addition, limited cytoplasmic autolysis is evident from 24 to 72 hr. A single injection of estradiol results in short-term nuclear receptor occupancy and elevated RNA polymerase activities which return to control levels by 24 hr. This collective evidence offers further support to the hypothesis that the duration of nuclear occupancy by the estrogen receptor is reflected in the size of the nuclear body populations in these epithelial target cells. Also during hyperestrogenization, epithelial hypertrophy is accompanied by steady formation of nuclear bodies.