Studies of the major histocompatibility complex (MHC) of cattle over the past twenty years have revealed a reasonably detailed picture of the genetic organisation and function of the genes within this genetic system. Serological and biochemical analysis of lymphocyte cell surface antigens provided the first evidence for highly polymorphic MHC genes in cattle and other ruminant species. The MHC of cattle was thus named the bovine leucocyte antigen (BoLA) system. During the past 10 years, tools of molecular biology have been used to characterise the number of MHC genes, their sequence and fine structure in a number of ruminant species. Although individual MHC genes were found to have clear orthologues among ruminants and other mammalian species, the MHC of cattle, and probably that of sheep and goats, has a unique genetic organisation. Cattle have a class II gene cluster (class IIb region) which is physically distant from all the other MHC genes on the same chromosome. Moreover, genes involved in antigen processing, such as the proteosome subunit locus LMP2, are also found in the class IIb region, demonstrating that these genes need not be in close proximity to other MHC genes to function normally. The MHC class I and class II gene products of ruminants present processed peptides to T lymphocytes which mediate helper and cytotoxic functions. Identification of peptide binding motifs of cattle MHC class I molecules indicates that ruminant MHC molecules function in a similar manner to those of mice and humans. These functional studies provide a firm molecular basis for a number of well-documented associations with infectious diseases, although a detailed understanding of the immunogenetic mechanisms underlying these associations has yet to be elucidated.