We have used cloned mouse and human heavy chain genes to identify regions of conserved homology between mouse and man and between mu and alpha genes. Using heteroduplex mapping, we find that coding segments for homologous domains appear to have been well conserved between the two species, but the short intervening sequences that separate domains have diverged considerably. These studies also identify extensive regions of homology 5' to both mu and alpha constant region genes that are conserved between the two genes as well as between mouse and man. These segments encompass regions in which mu/alpha recombination occurs during the heavy chain class switch, and their extensive homology may be relevant to this process.