Birds, like mammals, have highly a polymorphic MHC that determines strong allograft rejection. However, chickens have a much smaller, more compact and simpler MHC than mammals, as though the MHC has been stripped down to the essentials during evolution. The selection pressure on a single MHC gene should be much stronger than on a large multigene family, and, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. We have determined the peptide motifs for the dominant class I molecules from a number of chicken MHC haplotypes, which may explain some disease associations quite simply. Other disease associations, like the famous examples with Marek's disease, may be due to polymorphism in the level of expression of MHC class I molecules. We believe that the compact and simple nature of the MHC is due to the presence of microchromosomes in birds and suggest that the evolutionary origin of birds has been strongly influenced by the emergence of microchromosomes.