A thoroughly characterized breeding colony of 172 pedigreed rhesus macaques was used to analyze exon 2 of the polymorphic Mamu- DPB1, -DQA1, -DQB1, and - DRB loci. Most of the monkeys or their ancestors originated in India, though the panel also included animals from Burma and China, as well as some of unknown origin and mixed breeds. In these animals, mtDNA appears to correlate with the aforementioned geographic origin, and a large number of Mamu class II alleles were observed. The different Mamu- DPB1 alleles were largely shared between monkeys of different origin, whereas in humans particular alleles appear to be unique for ethnic populations. In contrast to Mamu-DPB1, the highly polymorphic - DQA1/DQB1 alleles form tightly linked pairs that appear to be about two-thirds population specific. For most of the DQA1/DQB1 pairs, Mamu- DRB region configurations present on the same chromosome have been ascertained, resulting in 41 different -DQ/DRB haplotypes. These distinct DQ/DRB haplotypes seem to be specific for monkeys of a determined origin. Thus, in evolutionary terms, the Mamu-DP, -DQ, and -DR regions show increasing instability with regard to allelic polymorphism, such as for -DP/DQ, or gene content and allelic polymorphism, such as for -DR, resulting in population-specific class II haplotypes. Furthermore, novel haplotypes are generated by recombination-like events. The results imply that mtDNA analysis in combination with Mhc typing is a helpful tool for selecting animals for biomedical experiments.