The HLA class I and class II loci are the most highly polymorphic coding regions in the human genome. Based on the similarity of the coding sequences of alleles between species, it has been claimed that the HLA polymorphism is ancient and predates the separation of human (Homo) and chimpanzee (Pan), 4-7.4 Myr ago. Analysis of intron sequences, however, provides support for a more recent origin and for rapid generation of alleles at the HLA class II DRB1 locus. The human DRB1 alleles can be divided into groups (allelic lineages); most of these lineages have diverged from each other before the separation of Homo and Pan. Alleles within such a lineage, however, appear to be, on average, 250,000 years old, implying that the vast majority (greater than 90%) of the more than 135 contemporary human DRB1 alleles have been generated after the separation of Homo and Pan. The coalescence time of alleles within allelic lineages indicates that the effective population size (Ne) for early hominids (over the last 1 Myr) was approximately 10(4) individuals, similar to estimates based on other nuclear loci and mitochondrial DNA. With a single exception, the genetic mechanisms (gene conversion and point mutation) that have diversified the exon-2 sequences do not appear to extend into the adjacent intron sequences. The part of exon 2 encoding the beta-sheet evolves in concert with the surrounding introns, while the alpha-helix appears to have been subjected to gene conversion-like events, suggesting that such exchange events are highly localised and occur over extremely short sequence tracts.