The effect of one, 4 and 8 weeks of continuous estrogenization of rabbit on peroxidase (PO) activity and on both cytoplasmic and nuclear estrogen receptors was studied in the uterus, vagina, urethra and urinary bladder. Whereas the peroxidase activity in the urogenital tissue of untreated controls was near zero, after one week of estrogen treatment it increased very substantially in the uterus and vagina and much less dramatically in the urethra or urinary bladder. With continuation of estrogen treatment for 4 or 8 weeks the PO decreased by 80-90% in the uterus and vagina and by only 40% in the urethra. After one week of estrogen treatment the density of both cytosolic and nuclear estrogen receptors decreased by several fold in both the uterus and vagina, whereas it decreased by 30-50% in the urethra and bladder. The concentration of both cytosolic and nuclear receptors decreased further although less dramatically with continuing estrogen treatment, up to 8 weeks, in all tissues. These data suggest that although the general pattern of responses to estrogen showing an initial increase in PO followed by a reduction with continuing estrogen treatment is the same in all urogenital tissues, the responses seem to have a prolonged time scale in the case of lower urinary tract tissues. The quantitative aspect of the response generally corresponds with the density of estrogen receptors in the urogenital tissues.