The constant rapid renewal of the epithelium of the gastrointestinal (GI) tract is important in the development of neoplasms that are derived from the epithelium as well as in maintaining the functional integrity of the mucosa. An abnormality of epithelial proliferation, characterized by an increase in numbers of proliferating cells and expansion of the proliferative zone, is common to all human premalignant conditions of the GI tract that have been studied, including Barrett's epithelium, chronic gastritis, ulcerative colitis, and colonic polyps, and is a consistent observation after the use of experimental carcinogens, such as N-methyl-N-amylnitrosamine and N-methyl-N'-nitro-N-nitrosoguanidine. These abnormalities also have been observed in some relatives of patients with colonic polyps or cancers who themselves do not have any demonstrable colonic lesion. Calcium, vitamins A, C, and E, and other agents have been shown to reverse the abnormalities in proliferation in some experimental and clinical conditions, which raises the question of whether some of these agents can be used to reduce the risk of development of cancer in patients with known premalignant conditions of the GI tract.