AbstractEstrogen action in the rat uterus can be arbitrarily considered as occurring in three steps. The first step is the interaction of the estrogen with the target tissue. This appears to be of stereospecific interaction with a receptor that is sensitive to proteinases and extremes of pH and insensitive to ribonuclease and deoxyribonuclease. The second step involves a change in the biological activity of this receptor protein due to the interaction with estrogen, a mechanism about which we have no definitive information at present. Eventually, this primary function does bring about an increase in glucose metabolism and an increase in lipid and RNA synthesis, as well as a number of other responses. The fact that these responses are all blocked by inhibitors of RNA and protein synthesis at a time when no effect on overall protein synthesis is noted suggests that the synthesis of specific enzymes may be involved. Certain complications in this interpretation are discussed. The events of the third, or amplification, step of estrogen action arise as a consequence of the first two events, and appear to include a number of metabolic changes which contribute to the increase in overall protein synthesis occurring between 2 and 4 hours after estrogen administration.