Cytotoxic peripheral blood lymphoid cells were demonstrated in both Holtzman and Lewis Brown-Norway rats which had received 2000R of local X-irradiation to the temporarily hypoxic, exteriorized, ileum and jejunum regardless of whether a small bowel adenocarcinoma subsequently developed. The cytotoxic response, which was detectable at two days, was quite evident by day 5 post-irradiation. No evidence of cross-reacting tumor antigens was obtained when similarly processed effector cells from Holtzman rats bearing a spontaneous mammary carcinoma were incubated with cell cultures derived from the small bowel adenocarcinoma. These findings indicate X-irradiation of the small bowel initiates lymphocyte sensitization that is manifested as in vitro cytotoxicity against cell cultures of the adenocarcinoma.