The present experiment was designed to determine whether sequential replacement of estrogen and progesterone to the ventromedial hypothalamus (VMH) would be sufficient to induce estrous behavior in ovariectomized rats. Bilateral cannulae containing 17β-estradiol (E2) diluted with cholesterol (1:250) were lowered into the VMH, preoptic area or midbrain and left in place for 4 days. On day 5, the E2 inserts were removed and P-filled cannulae were lowered into half of the subjects. The remaining females received systemic progesterone (500 μg). This steroid regimen was repeated 2 weeks later with the mode of progesterone administration reversed. All subjects were tested for estrous behavior twice after progesterone treatment. In a second experiment, <sup>3</sup>H-P:P-filled cannulae were lowered into the VMH of estrogen-primed females in order to estimate the extent of hormone spread from full-strength P-filled cannulae. Results indicated that estrogen and progesterone stimulation of the VMH is sufficient to activate estrous behavior in spayed female rats, however, precise localization of the hormone implants within the VMH is essential. 9 of the 11 females with both cannulae located within or at the border of the ventromedial nucleus (VMN) exhibited estrous behavior whereas only half of the females with only one implant resting in the VMN exhibited estrous responsiveness. Subjects with neither cannula located within or at the border of the VMN did not exhibit the behavior. The facilitative effects of P appeared to result from hormonal stimulation of the VMH and not from leakage of the steroid into other brain regions or into the systemic circulation. Following placement of tritiated progesterone implants into the VMH, high levels of radioactivity were recovered only from the mediobasal hypothalamus. The low levels of radioactivity measured in other brain regions, pituitary, uterus and blood indicate that relatively little if any hormone reached these tissues.