The DP region of the human major histocompatibility complex contains two alpha genes and two beta genes. The DP alpha 1 and beta 1 genes encode the expressed DP histocompatibility antigen molecule, while the DP alpha 2 and beta 2 genes are inactive in the haplotypes examined. Here we present the sequence of the two DP beta genes and of the expressed DP alpha 1 gene. Nucleotide sequence comparisons reveal a considerably greater degree of similarity between the two beta genes than between the two alpha genes. We propose that a duplication giving rise to the DP alpha gene pair evolutionarily preceded the corresponding DP beta gene duplication. We also propose, based on the orientation of other class II gene pairs, that the original DP molecule was encoded by the DP beta 1 and DP alpha 2 genes. At some stage during the evolution of the DP region both of the two pseudogenes appear to have been expressed.