Cynomolgus monkey is one of the macaque species currently used as an animal model for experimental surgery and medicine, in particular, to experiment new drugs or therapy protocols designed for the prevention of allograft rejection. In this field, it is of utmost importance to select histoincompatible recipient-donor pairs. One way to ensure incompatibility between donor and recipient is to check their major histocompatibility complex (MHC) genotypes at the loci playing a determinant role in histocompatibility. We report in this paper on the cynomolgus monkey DRB polymorphism evidenced by sequencing of amplified exon 2 separated either by denaturing gradient gel electrophoresis (DGGE), or by cloning. By the study of 253 unrelated animals from two populations (Mauritius and The Philippines), we characterized 50 exon 2 sequences among which 28 were identical to sequences already reported in Macaca fascicularis or other macaque species (Macaca mulatta, Macaca nemestrina). By cloning and sequencing DRB cDNA, we revealed two additional DRB alleles. Out of the 20 haplotypes that we defined here, only two were found in both populations. The functional impact of DR incompatibility was studied in vitro by mixed lymphocyte culture.