Cloned cDNA encoding the rat Sertoli cell receptor for FSH was isolated from a cognate library and functionally expressed in cultured mammalian cells. The FSH receptor (FSH-R), as predicted from the cDNA, is a single 75K polypeptide with a 348 residue extracellular domain which contains three N-linked glycosylation sites. This domain is connected to a structure containing seven putative transmembrane segments which displays sequence similarity to G protein-coupled receptors. Thus, the FSH-R is identical in its structural design to the LH/CG receptor (LH/CG-R). Furthermore, both receptors display 50% sequence similarity in their large extracellular domains and 80% identity across the seven transmembrane segments. Expression of the cloned cDNA in mammalian cells conferred FSH-dependent cAMP accumulation. The selectivity for FSH is attested by the fact that the related human glycoprotein hormones human CG and human TSH do not stimulate adenylyl cyclase in FSH-R expressing cells even when these hormones are present at high concentrations.