Our previous work has suggested that glucocorticoid pretreatment suppresses the enhanced responsiveness to GnRH seen in serum LH 12 h after castration. By contrast, serum FSH continues to show the castration-induced hypersensitivity to GnRH. Our attempts to replicate this LH suppression in static pituitary culture in vitro were not successful. This suggested to us the possibility that corticoids in vivo might be preventing castration-induced increases in pituitary GnRH receptor levels. We tested this at 24 h post-castration and, in fact, corticoids did not suppress the increase in GnRH receptors. In addition to the aforementioned effects of corticoids, we have seen that cortisol reverses the castration-induced drop in pituitary FSH content. It does this for 7 days post-castration, even though it no longer has an effect in suppressing serum LH. Thus, our accumulated data reveal that glucocorticoids have a differential effect on LH and FSH synthesis and secretion. Further studies are needed to clarify the site(s) of action of glucocorticoids in gonadotropin secretion and synthesis. Glucocorticoids may well prove to be a key in unlocking the mystery of the mechanism of differential control of regulation of LH and FSH.