The incidence of gastric, colonic, and rectal cancers was determined in a cohort of 73,076 men and women chronically immunosuppressed after heart or renal transplantation, to test the hypothesis that there would be a reduced incidence of gastric cancer by dampening chronic gastritis secondary to infection caused by Helicobacter pylori. Follow-up was from 1-13 years. No change in the incidence of gastric cancer was found (32 cases observed, 32.86 expected). An increase in colon cancer was found (75 cases observed, 62.27 expected). A significant reduction in the incidence of rectal cancer was found (15 cases observed, 41.5 expected). This led to a chi2 of 16.92 with 1 degree of freedom, significant at the 0.1% level. The effect was greater in men than women and more marked in heart recipients than in those receiving renal transplants. This unexpected finding led to a review of experiments in mice and rats that present evidence for immune promotion of large-bowel cancers induced by carcinogens by gut-associated lymphoid tissue. We conclude that an analysis of immune function in gut-associated lymphoid tissue in the stomach, colon, and rectum in healthy and immunosuppressed patients may lead to a better understanding of immunosurveillance in the colon and immune promotion of rectal cancers.