The purpose of this study was to characterize barrier function, hypoxic damage and prostaglandin levels in the urinary bladder in response to estrogen deficiency. Female New Zealand White rabbits were separated into three groups: ovariectomized; sham-operated; and ovariectomized treated with estrogen. Barrier function was compromised in the ovariectomized group compared to that of the sham group and the ovariectomized group treated with estrogen. Urinary bladders of ovariectomized animals showed higher concentrations of hypoxic markers than controls, localized primarily in the urothelium. Levels of 6-keto-PGF(1alpha) and PGF(2alpha) were significantly higher in smooth muscle than the ovariectomized animals and PGE(2) levels were significantly lower in the mucosa of ovariectomized animals. These results suggest that estrogen deficiency induces a loss of barrier function and an increase in hypoxia. The estrogen-dependent decreases of prostaglandin PGE(2) in the urothelium correlate with loss of barrier function, suggesting estrogen regulation of PGE(2) may contribute to maintenance of urothelial function.