Thirty complete coding sequences of human major histocompatibility com
plex (Mhc) class II DRB alleles, spanning 237 codons, were analyzed fo
r phylogenetic information using distance, parsimony, and likelihood a
pproaches. Allelic genealogies derived from different parts of the cod
ing sequence (exon 2, the 5' and 3' ends of exon 2, respectively, and
exons 3-6) were compared. Contrary to prior assertions, a rigorous ana
lysis of allelic genealogies in this gene family cannot be used to jus
tify the claim that the lineage leading to modern humans contained on
average at least 100,000 individuals. Phylogenetic inferences based up
on the exon 2 region of the DRB loci are complicated by selection and
recombination, so this part of the gene does not provide a complete an
d accurate view of allelic relationships. Attempts to reconstruct huma
n history from genetic data must use realistic models which consider t
he complicating factors of nonequilibrium populations, recombination,
and different patterns of selection.