Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH), regulates the reproductive hormonal cascade in vertebrates. Upon release from the hypothalamus, GnRH stimulates secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary. In humans, the type I GnRH receptor is a GPCR that is unusual in the lack of a cytoplasmic C-terminal tail. Although some species contain a type II GnRH receptor, the human version of this second receptor appears to contain mutations that render it inactive. GnRH analogs (agonists) are used in low doses in a pulsatile fashion in the treatment of infertility, delayed puberty and cryptorchidism. GnRH agonists at high doses desensitize the receptor, and are used along with antagonists in the treatment of hormone-dependent diseases (Millar et al., 2004). GnRH membrane preparations are crude membrane preparations made from our proprietary stable recombinant cell lines to ensure high-level of GPCR surface expression; thus, they are ideal HTS tools for screening of agonists and antagonists at GnRH. The membrane preparations exhibit a Kd of 0.3 nM for [125I]-[D-Trp6]-LHRH. With 10 mg/well GnRH Membrane Prep and 0.5 nM [125I]-[D-Trp6]-LHRH, a greater than 4-fold signal-to-background ratio is obtained.