The DR haplotypes of the human major histocompatibility complex have been arranged in five haplotypic groups based on genomic cloning and sequence analyses. To date, the expressed DRB sequences have been assigned to four different loci: DRB1, 3, 4 and 5. DRB1 alleles are present in all haplotypes, whereas DRB3, 4 and 5 are present only in some haplotypes. Here, Göran Andersson and colleagues suggest that DRB3, 4 and 5 sequences may be treated as a single allelic series. They argue that such a model is appropriate, since DRB3, 4 and 5 sequences are inherited in an allelic fashion, have similar genomic localization, exhibit similar levels of gene expression and are, with a few rare exceptions, not present in the same haplotype.