Serological approaches have been relatively unsuccessful in defining the allelic products of the bovine major histocompatibility (MHC) class II loci. We demonstrate that bovine class II allelic products can be characterized by precipitation with a polyclonal antiserum and separation using one-dimensional isoelectric focusing. Polymorphic beta chains were present in immunoprecipitates from both biosynthetically and surface-labeled lectin-stimulated bovine T cells. Precipitates from biosynthetically labeled but not surface-labeled T cells contained a basic invariant chain and a non-polymorphic structure. The non-polymorphic structure appears to be a beta chain. The polymorphic class II beta chain co-segregated with bovine MHC class I allelic products in a half-sibling family, providing evidence for linkage between bovine class I and class II loci. This approach to the biochemical analysis of the bovine class II structures should facilitate the investigation of the association between the bovine products and disease susceptibility.