Many murine T cell clones grow continuously in culture despite weekly ligation of their TCR by antigen. To learn how the cultured cells avoid or minimize antigen-induced cell death (AICD), we compared Fas and tumor necrosis factor (TNF) receptors (TNFR) on several long-term cultured CD8(+) T cell clones with those on naive and activated naive cells expressing the same TCR (2C). In contrast to the naive cells, Fas was absent on the cultured clones and the TNFR-II receptor, present initially at high levels on the cultured cells, was rapidly down-modulated in response to TCR ligation and had virtually disappeared by 2 h, when only approximately 10% of the cloned cells had been induced to express TNF-alpha. The extent of AICD of the cultured clones in response to cognate peptide-MHC on the presenting cells used for routine stimulation of the cultures was also considerably less than the massive cell death of the clones following exposure to anti-CD3 antibody plate-bound at high density.