ONE mechanism by which the immune system develops the ability to discriminate self from nonself is the deletion of autoreactive T-cell clones during thymic maturation^1–4. The drug cyclosporin A (CsA) has been shown to interfere with this process, allowing the escape of normally 'forbidden' T-cell clones^5,6 and the appearance of autoimmune disease^7–10. Recently, it has been demonstrated that immature thymocytes undergo programmed cell death (apoptosis) upon activation via the T-cell receptor¹¹. A similar phenomenon of activation-induced cell death (AICD) has been observed in T-cell hybridomas^12,13. Here we show that AICD in T-cell hybridomas in vitro and in thymocytes in vivo is blocked by CsA. Thus, clonal deletion may involve AICD when self-reactive, immature T cells are induced by self antigen, and CsA may cause autoimmunity by interfering with this process.