House mice (Mus musculus domesticus) avoid mating with individuals that are genetically similar at the major histocompatibility complex (MHC). Mice are able recognize MHC–similar individuals through specific odour cues. However, to mate disassortatively for MHC genes, individuals must have a referent, either themselves (self–inspection) or close kin (familial imprinting), with which to compare the MHC identity of potential mates. Although studies on MHC–dependent mating preferences often assume that individuals use self–inspection, laboratory experiments with male mice indicate that they use familial imprinting, i.e. males learn the MHC identity of their family and then avoid mating with females carrying ‘familial’ MHC alleles. To determine if female mice use familial imprinting, we cross–fostered wild–derived female mouse pups into MHC–dissimilar families, and then tested if this procedure reversed their mating preferences compared with in–fostered controls. Our observations of the female's mating behaviour in seminatural social conditions and the genetic typing of their progeny both indicated that females avoided mating with males carrying MHC genes of their foster family, supporting the familial imprinting hypothesis. We show that MHC–dependent familial imprinting potentially provides a more effective mechanism for avoiding kin matings and reducing inbreeding than self–inspection.