In association with luteinization, LH induces a decrease in the content of receptors for FSH and LH and an increase in that for PRL. To elucidate if the mechanism by which LH regulates its own receptors involved occupancy of sites and/or loss of receptors the effects of a luteinizing dose of LH were examined in the preovulatory follicles of immature hypophysectomized rats primed with estradiol and FSH. The measurable LH receptor content declined by 82% 24 h after LH administration. Serum concentration of the hormone declined by 24 h to 1.4% of the concentration measured 2 h after LH administration. Administration of iodinated LH to demonstrate occupancy of sites in vivo, resulted in a decline in the amount of hormone bound in vivo, over a period of time. This decline in occupancy paralleled the decrease in the number of available sites as measured in vitro. Furthermore, a large dose of highly purified hFSH administered in lieu of LH induced luteinization and an associated loss of gonadotropin receptors. These results indicate that luteinizing doses of LH and FSH induce a loss in gonadotropin receptors by mechanisms other than occupancy.