The glycoprotein hormone receptors differ from other G protein-coupled receptors by their large extracellular domain which mediates ligand binding. Cooperation between the G-protein coupled membrane domain, the extracellular domain and the hormone in establishing high-affinity binding and efficient transduction is likely to exist. Expression plasmids encoding the full-length porcine LH-hCG receptor (1-696), its extracellular (1-297) and membrane domain (298-696), as well as the alpha and beta subunits of hCG were constructed. We report that coexpression in COS cells of the two LH-hCG receptor domains restores cell surface high-affinity hormone binding and hormone dependent adenylyl cyclase activation, suggesting sufficient interactions between the two receptor domains to reconstitute a complete functional molecule. Moreover, the two hormone subunits and the two receptor domains are able to associate within coexpressing COS cells into an active complex.