Abstract Genes of the major class I and II histocompatibility complex have been extensively studied in mammals. Studies of these antigens in reptiles are very scarce. Here we describe the characteristics of these genes in the suborder Serpentes. We identified the presence of a much larger number of molecules of class I and beta chains of class II than found in mammals. Snakes only have one gene for the class II alpha chain. In these species, class I genes can be classified into two types. Approximately half of the genes lack 10 amino acids in the α 1 domain, producing a structural alteration in the interaction region with the T lymphocyte receptor. In the genome of Thamnophis elegans , two haplotypes of an individual were studied revealing a different number and location of class I genes between these haplotypes. The results indicate that in these species, the diversity in the MHC is generated by the presence or absence of genes, independent of the presence of alleles.