The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat femoral cortical bone. Ninety-two 11-month-old female Sprague-Dawley rats were randomly divided into six groups and were treated for a duration of 6 months. Group-1 rats were intact controls, group-2 rats were ovariectomized controls, and groups 3-6 were ovariectomized and given continuous doses of estrogen with 5% estradiol 17B silicone-rubber implants. Groups 4, 5, and 6 were also given different doses of progestin (norethindrone): group 4 received a continuous dose of 3 micrograms per animal per day, group 5 received a cyclic dose of 6 micrograms per animal per day for 14 days of a 28-day cycle, and group 6 received an interrupted dose of 3 micrograms per animal per day for 3 days of a 6-day cycle. Femurs from each group were mechanically tested. Bending stiffness was measured by nondestructive three-point bending tests and maximum torque capacity, by destructive torsion tests. Geometrical properties and apparent density of cortical bone were also measured. The significant differences were: the increases in elastic modulus (measured from the three-point bending stiffness) of group 5 (cyclic norethindrone) compared with those of group 2 (ovariectomized controls) and group 3 (estrogen only); the increases in the size represented by the moment of inertia, the moment of the area, and medial-lateral width of group 2 compared with those of group 5; and the increases in apparent density and decreases in moment of inertia of group 6 (interrupted norethindrone) compared with those of group 2. Cyclic or interrupted treatment of progestin along with continuous treatment of estrogen after ovariectomy likely improves material properties of cortical bone, increases its density, and reduces the size of the bone compared with ovariectomized rats.