The products of the major histocompatibility complex (MHC) loci regulate an individual's immune response to pathogens. Cattle provide an important model to study the relationship between disease susceptibility and MHC haplotype since large half-sibling families are common. The definitive demonstration, however, of a firm relationship between MHC phenotype and disease susceptibility in cattle will require a precise definition of the bovine MHC allelic products. Available reagents for serological characterization of the bovine MHC gene products have not been adequate for these purposes. We have shown that existing mouse monoclonal antibodies and rabbit anti-human antisera precipitate bovine class I molecules, that these structures separate well by one-dimensional isoelectric focusing (1-D IEF), and that immunoprecipitation followed by 1-D IEF allows the detection of bovine class I MHC allelic products. Through this technique, we have identified previously undetected class I products. This approach will facilitate a detailed characterization of the bovine MHC class I gene products.