It has been suggested that oral tolerance is mediated by CD8⁺ T lymphocytes, but the functional properties of these cells are unclear. Here we show that the induction of tolerance by feeding mice ovalbumin (OVA) does not prime antigen-specific class I MHC-restricted cytotoxic T cells in vivo. Indeed, such responses are markedly suppressed in mice fed OVA, and the induction of oral tolerance is abolished by depletion in vivo of CD4⁺ but not CD8⁺ T cells. These results indicate that CD8⁺ lymphocytes are unlikely to play a major role in the induction of oral tolerance and are the first demonstration that specific cytotoxic responses to an exogenous antigen can be suppressed by feeding antigen.