TNF receptor‐ligand interactions and CD95 (Fas / APO‐1) have been demonstrated to be involved in activation‐induced death of mature T cells. Here, we examined the role of these molecules in the murine model of lymphocytic choriomeningitis virus (LCMV) infection using LCMV TCR transgenic (tg) mice lacking TNF, TNF receptor I (TNFR1), CD95 or both TNFR1 and CD95. This report demonstrates that neither TNF receptor‐ligand interactions nor CD95 was required for down‐regulation of LCMV‐specific CD8 T cells following acute LCMV infection in vivo. Even LCMV‐specific CD8 T cells lacking both TNFR1 and CD95 molecules declined after the acute phase of the infection with normal kinetics. Furthermore, peripheral deletion of LCMV‐specific CD8 T cells induced by LCMV peptide injection or by adoptive transfer of tg spleen cells expressing the corresponding LCMV epitope was not impaired in mice lacking TNF, TNFR1 and / or CD95. Our data speak against an indispensable role of these molecules in antigen‐induced apoptosis of CD8 T cells in vivo and suggest that T cell homeostasis after antigen challenge is controlled by additional mechanisms.