Changes in uterine weight and the estrogen receptor concentrations were examined in persistent estrous (PE) and persistent diestrous (PD) rats at 80 days of age. To prepare PE rats, 100μg estradiol benzoate (EB) was injected sc into 3-day-old females. PD rats were obtained by daily injections of 10μg EB into females for 10 consecutive days from the day of birth. The uterine weight in PE rats at 80 days was comparable to that in metestrous controls. The uteri of PD rats were smaller than those in PE rats. The concentrations of estrogen receptor in nuclear fractions in PE and PD rats were much lower than those in proestrous controls. Receptor concentrations in cytosol fractions were significantly lower in PE and PD rats than in control diestrous, proestrous and estrous rats. The dissociation constants and sedimentation coefficients of estrogen receptors in PE and PD rats were found to be in the same range as those in control rats. Thus, the reduction in the activity of cytosol receptors in these rats is attributable to a quantitative change in the amount of estrogen receptor protein. To study the response of the uterus to estrogen, ovariectomized rats were injected daily with 10 pg estradiol for 7 consecutive days. The uterine growth of PE and PD rats after administration of estradiol was less marked than in controls, indicating a reduction of estrogen sensitivity of the uterus. Seven daily administrations of estradiol continued to increase the concentration of uterine cytosol estrogen receptor in controls. In contrast, in PE and PD rats, the receptor concentrations continued to increase during the first 3days.and then remained constant.These data suggest that EB in neonatal treatment may directly affect the mechanism of receptor synthesis in uterine tissues. This effect may contribute to the reduction of the uterine response to estrogen.