The genomic nucleotide sequences of HLA-DMA and HLA-DMB have been determined and their gene organizations have been compared with other human class II genes. The following features were found to be highly conserved throughout all human class II families. (i) All alpha genes are composed of 5 exons and all beta genes of 6 exons. (ii) The intron-exon boundary classes of exons 1-4 (alpha genes) and exons 1-5 (beta genes) are 100% conserved. Only the last boundary class which falls within the cytoplasmic domain appears to be variable. (ii) The size of exon 3 (membrane proximal domain) is also 100% conserved except for DMA (-1 codon) and DMB (+1 codon). The position and a possible functional implication of this deletion/insertion are discussed. Our findings confirm and extend the evidence based on sequence homology that DMA and DMB are different from typical class II genes suggesting that they may originate from a time prior to the divergence of the main class II genes. In addition we have identified various new repeat sequences within class II genes. Analysis of their classification and distribution reveal single and multiple repeat mediated recombination events. One of these events seems to have partially replaced exon 1 in DPA2. The possibility of this event causing DPA2 to become a pseudogene is discussed.