In principle, the function of major histocompatibility complex (MHC) molecules is simple : to bind a peptide and engage a T cell. In practice, placing this function within the context of the immune response begs questions of population biology : How does the immune response emerge from the interactions among populations of peptides, T cells, and MHC molecules? Within a population of vertebrates, how does MHC polymorphism stamp individuality on the response? Does polymorphism confer differential advantages in responding to parasites? How ale the pressures on the MHC reflected in turnover of alleles? The role of mutation, recombination, selection, and drift in the generation and maintenance of MHC class I polymorphism are considered.