Experiments were performed to examine the uterine response to estrogen and the dynamics of uterine estrogen receptor in adult ovariectomized mice given estrogen injections neonatally. Uterine tissue of neonatally estrogenized mice showed a markedly reduced response to estrogen in the adult. The concentration of cytoplasmic estrogen receptor in the uteri of such mice was markedly lower than that of neonatally vehicleinjected control mice. Nuclear and cytoplasmic estrogen receptors of uteri in both groups were determined by the exchange assay at various intervals after injection of estradiol. Nuclear translocation of estrogen receptor complexes in neonatally estrogenized mice was similar to that in control mice. The concentration of cytoplasmic receptor decreased to low levels by 1 h and began a gradual increase from 1–16 h after injection in both groups. Between 16–24 h after injection, however, the level of cytoplasmic receptor continued to increase in control mice but almost ceased to increase in neonatally estrogenized mice. Ten daily injections of estradiol continued to increase the concentration of cytoplasmic estrogen receptor in control mice. On the other hand, in neonatally estrogenized mice treated daily with estradiol, the receptor level reached a plateau on day 5. These data suggest that the induction of new uterine estrogen receptor under the influence of estrogen may be altered by neonatal estrogen treatment.