Productive immune responses require an appropriate environment to support peripheral CD8⁺ T cell survival. Although host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase‐activating gene‐2 (RAG‐2)^–/– TCR‐transgenic T cells, we found that the survival of both naive and effector CD8⁺ T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class Iby either bone marrow‐ or non‐bone‐marrow‐derived cells was sufficient, suggesting that professional antigen‐presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM‐1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by overexpression of Bcl‐x_L by CD8⁺ T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8⁺ T cells die via a Fas‐dependent, mitochondria‐independent pathway.