We report that, in peripheral blood T cells, the V beta 8 gene product is much more represented on CD4+CD8- than on CD4-CD8+ lymphocytes. This skewing was observed in all individuals tested and with two independent strategies, one of which allows the selection of V beta 8+ T cells independently from their major histocompatibility complex-antigen specificity. Our data imply that the human V beta 8 gene product confers class II restriction specificity and that both the T cell receptor chains and CD4 molecule are involved in the selection of the T cell repertoire.