Extensive polymorphism at the major histocompatibility complex (MHC) is thought to confer immune protection on populations. A New World primate, the cottontop tamarin (Saguinis oedipus), has a high prevalence of ulcerative colitis and adenocarcinoma of the colon and dies after infection with several human viruses. Lymphocytes from all animals tested expressed one common MHC class I allelic product. Another MHC ciass I allelic product was expressed by 39 of 41 tested animals. Four other ailelic products were also expressed on the lymphocytes of these animals at a frequency of >50%. MHC class II gene products, however, were polymorphic. Restriction fragment length polymorphism analysis confirmed that there were a limited number of cotton-top tamarin MHC class I alleles, whereas the MHC class II gene loci were polymorphic. This sharing of MHC class I alleles is unprecedented in a higher primate species and may play a role in the susceptibility of this endangered species to pathogens.Major histocompatibility complex (MHC) glycoproteins play an important role in immune cell interactions. Codominant expression of class I and class II allelic products and an extraordinary degree of polymorphism of these products in a species are thought to confer a survival advantage to individuals and to the species by facilitating the ability of the immune system to interact with a variety of pathogens.Cotton-top tamarins (Saguinus oedipus) are highly susceptible to a variety of pathogenic processes. As many as 60% of captive S. oedipus spontaneously develop ulcerative colitis and 15% of these animals develop adenocarcinoma of the colon (1). S. oedipus also develops fatal lymphoproliferative syndromes after infection with Epstein-Barr virus and Herpesvirus saimiri (2, 3). Additionally, these tamarins are highly susceptible to retrovirus-induced sarcomas and fatal measle virus infections (3). Interestingly, cotton-top tamarins are usually born as dizygotic twins and an anastamosing placental circulation results in their development as naturally occurring bone-marrow-chimeric animals (4).In this study, we demonstrate that the cotton-top tamarin possesses very few allelic products at its three MHC class I loci. Its MHC, however, encodes for a diversity of class II allelic products, suggesting that its limited number of class I alleles are not due to a recent founder effect. This unprecedented limited MHC class I polymorphism in a primate species may play a role in the cotton-top tamarin's extreme susceptibility to pathogens. Celi Culture. Peripheral blood lymphocytes (PBLs) were separated from 2 to 10 ml of heparinized blood by using Dextran or Ficoll/diatrizoate gradient centrifugation. These cells were cultured at 106 cells per ml with phytohemagglutinin-P (Difco) at 1 pug/ml in RPMI 1640 medium (GIBCO) supplemented with heat-inactivated fetal bovine serum (Sterile Systems, Logan, UT) to a final concentration of 10% (vol/vol), 2 mM L-glutamine, 50 1LM 2-mercaptoethanol, 20 mM Hepes, gentamycin at 40 ,ug/ml, amphotericin B at 0...