The DQA1 and DQB1 alleles of 258 rhesus monkeys (Macaca mulatta) of different origin were typed by PCR-RFLP. Five novel MamuDQA1 and five novel -DQB1 alleles were detected and 15 Mamu-DQA1-DQB1 haplotypes were identified. Haplotype analysis confirmed the conservation of the DQA1*01-DQB1 *06 haplotypes in evolution. The most conspicuous finding was the tight linkage between the Mamu-DQA1 and -DQB1 alleles. Almost in every case the Mamu-DQA1 allele was linked to only one particular Mamu-DQB1 allele. Although there also are constraints in the formation of DQ haplotypes in humans, such tight linkages are not observed. These findings support the hypothesis of some kind of co-evolution between DQA1 and DQB1 alleles and may reflect a stronger force of natural selection in macaques than in humans.