Background: The anti-androgen (flutamide) is widely used nowadays in the treatment of cancer prostate either alone or in combination with Luteinizing Hormone Releasing Hormone (LHRH) analogues. These drugs block androgen receptors, thus prevent growth of cancer cells. Meanwhile, gonadotroph cells of the anterior pituitary may be affected. Aim of the work: To study the effects induced by flutamide administration in the presence or absence of concomitant use of LHRH analogue on gonadotrophs. Materials and methods: Twelve adult male albino rats were divided into three groups: Group (I) rats were served as controls, Group (II) rats were given flutamide orally while Group (III) rats were given flutamide combined with LHRH analogue. The experiment lasted for 20 days after which the rats were sacrificed and pituitary glands were collected. Samples were processed for Hx.&E., immunohistochemistry and electron microscope examination. Results: Gonadotrophs of Group (II) rats showed cytoplasmic vacuolation, castration cells, increased vascularization and decreased immunoreactive cells.  E/M examination revealed reduction of secretory granules and dilatation of rER. Morphological changes of nuclei and disappearance of cell membrane were demonstrated.  In rats of Group (III), some cells appeared normal while others showed cytoplasmic vacuolation with increased immunoreactive cells compared to Group (II). In E/M examination, most of the rER returned to normal appearance with partial sparing of secretory granules. Most cells showed normal nuclei. Conclusion: Flutamide produced marked histological, immunohistochemical and ultrastructural changes of pituitary gonadotroph cells similar to castration effects which were improved by concomitant use of LHRH analogue.