T-CELL receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apol/CD95) and Fas ligand (FasL)^1-12. Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively^13,14. However, peripheral T-cell deletion takes place in lpr mice, and autoimmune syndromes occur in mouse strains without Fas or FasL defects^15,16. Here we show that tumour necrosis factor (TNF) can mediate mature T-cell receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and FasL is required to abrogate T-cell death and TNF mediates the death of most CD8⁺ T cells, whereas FasL mediates the death of most CD4⁺ T cells. Our results suggest that autoregulatory apoptosis of the mature T cells can occur by two distinct molecular mechanisms.