The major histocompatibility complex (Mhc) is a multigene family found in vertebrates. Mhc genes code for heterodimeric cell-surface molecules involved in presentation of peptides to T-lymphocytes. There are two classes of Mhc, and in eutherian mammals four main families of class II genes have been recognized; DR, DQ, DP, and DN/DO. Each class II family contains genes that code for one or more alpha and beta chains. Do the class II genes of marsupial mammals belong to any of these eutherian mammal class II families? The results to date are conflicting. The expressed class II beta-chain genes could not be satisfactorily assigned to any eutherian class II gene family and were designated as new gene families, while, conversely, a partial sequence of an expressed alpha-chain gene was clearly very similar to the DNA gene of eutherian mammals. The aim of this study was to conduct a more thorough analysis of the alpha-chain genes in a marsupial by obtaining full-length sequences of all the expressed alpha-chain genes in the red-necked wallaby, Macropus rufogriseus. Two class II alpha-chain genes were isolated from a spleen-derived cDNA library, and both have the potential to code for fully functional MHC molecules. Phylogenetic analysis indicated they belonged to previously identified eutherian class II families and are designated as Maru-DRA and Maru-DNA. Northern blot data indicated processed transcript sizes of approximately 1.6 kb for Maru-DRA and approximately 2.5 kb for Maru-DNA and that the latter was expressed at a lower level than the former. The phylogeny shows that the DR, DQ, DP, and DN/DO gene families diverged prior to the divergence of the marsupial and eutherian mammal lineages.