MIC genes map to the major histocompatibility complex (MHC) and are distantly related to MHC class I genes. Recently, MICA/MICB-like genes have been described in nonhuman primates. In Macaca mulatta, three MICA/B-like genes could be identified: Mamu-MIC1, Mamu-MIC2, and Mamu-MIC3. We show here the isolation and characterization of rhesus macaque cosmid clones which carry the Mamu-MIC2 and Mamu-MIC3 genes. Neither the MIC2- and MIC3-coding sequences nor respective flanking sequences can be aligned unambiguously to either the human HLA-MICA or -MICB subregions, although MIC2 was found at a similar distance to the BAT1 gene as known for MICB in human. Thus, the characteristics allowing for a classification of primate MIC genes as being of the MICA or MICB types appear to have evolved after the separation of humans and rhesus monkeys from a common ancestor. Furthermore, also Mamu-MICD-containing cosmids could be isolated. In contrast to Mamu-MIC2 and Mamu-MIC3, the Mamu-MICD gene and its flanking sequences are highly conserved and orthologous to the human MICD subregion.