The HLA (human major histocompatibility complex, or MHC) region includes three types of class I MHC genes: (1) class Ia loci (HLA-A, -B, and -C), which are highly expressed and polymorphic; (2) class Ib loci, which have much reduced expression and polymorphism; and (3) unexpressed class I pseudogenes. Phylogenetic analysis suggests that both class Ib loci and class I pseudogenes arose by duplication of class Ia loci. 5' regulatory elements conserved in class Ia genes are not conserved in either class Ib or class I pseudogenes, but the former show evidence of purifying selection at nonsynonymous sites in coding regions that is lacking in the latter. In the HLA class I region, there is little correspondence between map distance and phylogenetic distance, suggesting a complex history of tandem gene duplications. Furthermore, separate phylogenetic analysis of different gene regions suggests that several class I genes are evolutionary chaemeras, which presumably have arisen as a result of a process of interlocus recombination. For example, the 5' flanking region of the HLA-92 pseudogene was donated by a gene related to HLA-B and -C; and the HLA-A gene arose when exons 1-3 (and intervening introns) were donated to a gene related to the HLA-70 pseudogene by a gene related to HLA-B and -C.