Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies suggest that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats that had been subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included: sham ovariectomy (shamOVX), ovariectomy (OVX), OVX with estrogen replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed with repeated cystometrograms (CMG) to measure micturition thresholds (MT) before and hourly for 3 hours after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX group. As expected, bladder inflammation induced bladder hyperreflexia in shamOVX rats (studied in estrus). This hyperreflexia was eliminated by OVX and restored by both estradiol replacement and by HYPX. Combining estradiol replacement and HYPX (i.e., OVX+E+HYPX) did not increase the severity of bladder hyperreflexia compared with either manipulation alone. These results indicate that the bladder hyperreflexia that is induced by bladder inflammation requires the presence of estradiol, and suggest that this hormonal modulation is exerted via the sympathetic control of the bladder, possibly via an increase of beta-adrenergic inhibitory actions on the detrusor muscle. Similar mechanisms may contribute to bladder disorders in postmenopausal women.