The aim of this work is to determine the DNA sequence organization of class I genes contained in the swine major histocompatibility complex (SLA). It has been demonstrated that there are a total of 10-15 class I MHC genes in the swine genome. A series of genomic clones containing MHC-homologous DNA sequences has been isolated from both genomic lambda and cosmid libraries. Detailed DNA sequence analysis of two of the MHC genes is currently in progress. Our studies to date indicate that swine class I genes consist of 8 exons encoding distinct functional domains of the SLA antigen: leader polypeptide, three extracellular domains, a transmembrane domain, and intracytoplasmic domains. Comparison of the two swine class I genes inter se indicates a strong conservation of both overall organization and DNA sequence. Comparison of these two sequences with known human MHC genes suggests different regions of the gene are subject to different evolutionary constraints: either allele specific or species specific. Further analysis of these gene sequences should shed light on the evolution of this multigene family and the generation of polymorphism.