The common marmoset (Callithrix jacchus) is a New World primate species that is highly susceptible to fatal infections caused by various strains of bacteria. We present here a first step in the molecular characterization of the common marmoset’sMhcclass II genes by nucleotide sequence analysis of the polymorphic exon 2 segments. For this study, genetic material was obtained from animals bred in captivity as well as in the wild. The results demonstrate that the common marmoset has, like other primates, apparently functionalMhc-DRand -DQregions, but theMhc-DPregion has been inactivated. At the -DRand -DQloci, only a limited number of lineages were detected. On the basis of the number of alleles found, the -DQAand -Bloci appear to be oligomorphic, whereas only a moderate degree of polymorphism was observed for two of threeMhc-DRBloci. The contact residues in the peptide-binding site of the Caja-DRB1*03 lineage members are highly conserved, whereas the -DRB*W16 lineage members show more divergence in that respect. The latter locus encodes five oligomorphic lineages whose members are not observed in any other primate species studied, suggesting rapid evolution, as illustrated by frequent exchange of polymorphic motifs. All common marmosets tested were found to share one monomorphic type ofCaja-DRB*W12allele probably encoded by a separate locus. Common marmosets apparently lack haplotype polymorphism because the number ofCaja-DRBloci present per haplotype appears to be constant. Despite this, however, an unexpectedly high number of allelic combinations are observed at the haplotypic level, suggesting thatCaja-DRBalleles are exchanged frequently between chromosomes by recombination, promoting an optimal distribution of limitedMhcpolymorphisms among individuals of a given population. This peculiar genetic make up, in combination with the limited variability of the major histocompatability complex class II repertoire, may contribute to the common marmoset’s susceptibility to particular bacterial infections.