Two large and divergent families of G-protein-coupled receptors (V1Rs and V2Rs) are expressed in subsets of neurons in the vomeronasal organ. These receptors are likely to mediate pheromone responses, but it appears that many V2R genes may encode expressed pseudogenes rather than functional proteins. Therefore we have raised antibodies to representative V2Rs and show labeling of vomeronasal neurons demonstrating that V2R genes encode expressed receptors. V2R immunoreactivity was detected at the sensory surface of the vomeronasal organ in dendritic terminals, indicating that these receptors are capable of directly interacting with pheromones and mediating physiological responses. Immunohistochemistry confirmed that three V2R receptors are expressed in small subsets of sensory neurons. However, surprisingly we found that a subfamily of V2R genes is broadly expressed in the Goalpha-layer of the vomeronasal organ and are coexpressed in the same cells as other V2Rs. This is in direct contrast to the main olfactory epithelium where sensory neurons express only a single receptor. Thus, our results suggest that different modes of the information processing may occur in the main and accessory olfactory systems.