Major histocompatibility complex (MHC) molecules have been implicated in a number of non-immune roles in the central nervous system, particularly in synaptic development and plasticity. The discovery of M10 (50% sequence identity to classical MHC molecules) proteins expressed in the vomeronasal organ adds to the list of non-traditional roles of MHC homologs. M10 molecules associate with the V2R class of vomeronasal receptors, a family of G-protein coupled receptors thought to function as pheromone receptors. Recent studies showing that classical MHC-binding peptides activate V2R-expressing neurons offer tempting clues that M10s might participate directly in the recognition of pheromone ligands, but M10 proteins do not bind to these peptides with significant affinity. Instead of presenting MHC-binding peptides, M10s might function as molecular chaperones to V2R receptors or more generally as modulators of neuronal function, as demonstrated elsewhere in the brain for classical MHC molecules.