The ability of antigens administered by the intestinal route to alter the cytotoxic T lymphocyte (CTL) population in intestinal and extraintestinal sites was examined by feeding mice tumor cells bearing H-2 or non-H-2 genecoded cell surface alloantigenic differences. Peyer's patches from mice fed tumor cells differing at H-2 demonstrated a 12-fold increase in specific CTL activity over controls after stimulation in culture but the precursor CTL population in Peyer's patches was not expanded by feeding mice cells bearing minor H gene coded alloantigenic differences. In contrast, the precursor CTL pool in spleen was increased both in mice fed cells bearing alloantigenic differences coded for by H-2 and non-H-2 gene loci. The precursor CTL population in mesenteric lymph nodes (MN) was not expanded significantly by tumor cell feeding. Feeding was nearly as effective as i.p. priming at expanding the Peyer's patch precursor CTL population when tumor cells bearing H-2 differences were used, whereas i.p. priming was more effective than feeding in expanding the precursor CTL population in spleen.