The direct effects of median eminence extract (MEE), estradiol (E) or progesterone (P) or combinations of these hormone preparations on the structure of the adenohypophysis and its secretion of gonadotrophins were examined in female rats bearing pituitary homografts obtained from long-term ovariectomized (LTO) donors. Preliminary investigation had shown that the pars distalis of LTO animals retained large numbers of hypertrophied gonadotrophs for several weeks even when homografted under the kidney capsule of hypophysectomized recipients. Homografts from vehicle-treated controls contained many gonadotrophs at 24 days. Treatment with E or P resulted in complete disappearance of gonadotrophs at 24 days, but not at 10 days. E produced depletion of gonadotrophs even in the presence of MEE, while P + MEE treatment resulted in retention of gonadotrophs. In general, ovarian morphology correlated well with changes in pituitary cytology. These results suggest that the ability of MEE to stimulate release (and probably synthesis) of gonadotrophic hormones depends on the steroid sensitization of pituitary tissue and the differential effect of E and P on gonadotrophin release in the presence of MEE.