Using TCR-specific mAbs, we analyzed the TCR distribution in the CD4 and CD8 compartments of peripheral blood T cells from members of six families, including two which were informative for an HLA-B/DR crossover. TCR distribution in the CD4 compartment is influenced by MHC class II antigens as it was similar in the child carrying the HLA-B/DR recombination and in the HLA-DR-identical sibling. There was also a relatively small degree of difference between TCR distribution in the CD8 compartment of a child with an HLA-B/DR crossover and his HLA class-I-identical sibling. Analysis of TCR Vβ gene usage in the CD4 compartment of unrelated individuals sharing an HLA-DR allele showed an increased usage of Vβ8a and Vβ12a in DR4-positive subjects. These data suggest that studies of TCR Vβ gene usage in individuals with HLA-associated autoimmune diseases may provide further information about MHC-dependent biases in the T-cell repertoire.