Nonresponsiveness of mammalian T cells to self-antigens is not totally accounted for in terms of clonal deletion, T-cell anergy and T-cell ignorance: studies have shown that the T-cell repertoire of healthy individuals contains cells with the potential to cause autoimmune disease. This article describes a T-cell-mediated mechanism that prevents the realization of this potential and indicates how its failure can lead to the development of autoimmunity.