Mucosal tissues of mice are enriched in 16 T cells; however the function of these cells remain unclear. Thus, we have compared mucosal immune responses in 76 T cell receptor deficient (TCRS'/") mice versus control mice of the same genetic background. The numbers of intestinal IgA plasma cells as well as IgA levels in serum, bile, saliva and fecal samples were markedly reduced in TCR8''' mice. The TCR5"'- mice produced much lower titers of IgA antibodies when immunized orally with a vaccine of tetanus toxoid plus cholera toxin as adjuvant. Conversely, the antigenspecific IgM and IgG antibody responses were comparable to orallyimmunized, control mice. Direct assessment of the cells forming antibodies against tetanus toxoid and cholera toxin indicated that a significantly lower frequency of IgA antibody producing cells were present in the intestinal associated tissues of TCR8-'- mice when compared with orally-immunized control mice. The selective reduction of IgA responses to ingested antigens in TCR8''- mice suggests a specialized role for v8 T cells in mucosal immunity.