The factors controlling memory T (Tm)-cell longevity are still poorly defined, and their identification is pivotal to the design of a vaccine conferring long-term protection against infection. Tm cells have the ability to survive in the absence of the T-cell receptor (TCR)-MHC interaction. This does not exclude a possible role for TCR-intrinsic ligand-independent constitutive signaling in Tm-cell homeostasis. Using a unique TCR tetracycline-inducible expression system, we show that the ablation of TCR expression, which abrogates any possible signaling via the TCR, did not influence the survival and self-renewal of antigen-specific CD8(+) Tm cells even when they have to compete with endogenous T cells for survival factors. Moreover, CD8(+) Tm-cell functionality was not altered even on prolonged maintenance in the absence of TCR-MHC interactions. Furthermore, our results show that a subset of CD4(+) Tm cells can survive in the absence of TCR expression in nonlymphopenic hosts.