Urethral pressure profiles (in vivo), opening pressures, and flow rates at opening pressure (in vitro) were determined for female, male, pregnant, ovariectomized (OVX), OVX and then estrogen-treated, and OVX and then progesterone-treated rabbits. Using the isolated whole-urethra preparation, we determined the opening pressures and flow rates as well as the effects of 250 microM phenylephrine, 250 microM bethanechol, and 120 mM KCl on the urethral opening pressure and flow rate. The results demonstrated that (1) the urethral pressure profiles were similar for male and female rabbits, (2) ovariectomy and pregnancy decreased the urethral pressure profiles, (3) estrogen therapy partially reversed the effect of ovariectomy on the urethra, and (4) progesterone therapy had little effect on the urethral pressure profile. With regard to opening pressure and flow, (1) flow at opening pressure was lower in the male than in the female; (2) the opening pressure was increased by ovariectomy; (3) phenylephrine and KCl stimulated a greater response in the male than in the female, whereas the response to bethanechol was significantly lower in the male than in the female; (4) the male had the greatest resistance to flow among all the groups; and (5) ovariectomy increased the resistance to flow and estrogen treatment reversed the effect of ovariectomy. In conclusion, ovariectomy had significant effects on urethral function that were reversed by estrogen therapy but not by progesterone therapy.