CLONAL deletion and functional inactivation of self-reactive cells have been invoked as mechanisms underlying intrathymic development of T-cell tolerance^1–10. The relative importance of these mechanisms in the development of tolerance of more mature, peripheral T cells either to self or to exogenous antigens is unclear, although recent data relate the development of T-cell tolerance in the periphery to clonal anergy¹¹. We have now investigated the induction of extrathymic tolerance using BALB/c mice that were made tolerant to Staphylococcus aureus enterotoxin B (ref. 12), a superantigen which specifically interacts in such mice with T cells bearing Vβ8 antigen receptors^13–16. Both euthymic and athymic mice made tolerant to S. aureus enterotoxin B had a markedly reduced number of Vβ8.1,2⁺ CD4⁺ peripheral T cells. This reduction was accompanied by genomic DNA fragmentation that is associated with cell death. These results indicate that a deletional mechanism can contribute to the induction of T-cell tolerance in peripheral lymphoid cells.