The extent to which alleles can disperse across a hybrid zone depends on the selection they are subjected to in the hybrid genetic background or, for those that are selectively neutral, on their ability to escape from the unfavourable environment by recombination. Three markers spanning a 45 cM segment in the center of the X chromosome were used to investigate the degree to which selection against X chromosome linked genes helps to maintain the barrier to gene flow in the hybrid zone between Mus musculus domesticus and M. m. musculus in Denmark. The introgression of all the sex chromosome specific markers was more limited than that of the autosomal enzymes (Idh1, Amy, Gpd1, Pgm1, Es1, Es2, Mpi, Np1, Es10, Sod1) and the mitochondrial DNA. The cline for DXPas2, which is in the center of the X chromosome, is extremely steep and shows that certain genes located in this region are strongly selected against in the hybrid background. The clines of the other two X-linked markers, Hprt and DXPas1, and of the Y chromosome are not as abrupt and all three have similar asymmetric introgression patterns. Although the musculus variants appear to behave in much the same way as those of the autosomal genes, the domesticus variants do not introgress. The results show that X-linked and to a lesser extent Y-linked genes are more strongly selected against in the hybrid genome than the mitochondrial genome or the different autosomal loci. This suggests that co-adapted gene systems involving the sex chromosomes may play an important role in the hybrid breakdown between the two subspecies.