The vomeronasal organ (VNO) mediates detection of pheromones related to social and reproductive behavior in most terrestrial vertebrates. We have identified a new multigene family of G protein-linked receptors (V2Rs) that are specifically expressed in the VNO. V2Rs have no significant homology to other putative pheromone receptors (V1Rs) or to olfactory receptors but are related to the Ca2+-sensing receptor and metabotropic glutamate receptors. V2Rs are expressed at high levels in small subpopulations of VNO neurons. V2Rs are primarily expressed in a different layer of VNO neurons from V1Rs, thus both gene families are likely to encode mammalian pheromone receptors.