Signals that control normal and neoplastic epithelial proliferation are not completely understood. We have reviewed the importance of the possible roles of the following control mechanisms: polyamine biosynthesis, intraluminal nutrients, gastrointestinal hormones and growth factors, bowel resection, carcinogens, and oncogenes. The mechanisms by which these agents act and the precise roles they play in normal and abnormal proliferation of intestinal mucosa have not yet been clearly defined. Peptide hormones and growth factors exert their mitogenic effects by first interacting with specific receptors in the cell membrane. Oncogenes induce production of growth factors or replace growth factors and, by themselves, stimulate growth. We believe that no single agent is likely to be responsible; rather, multiple agents are involved in stimulation of growth of normal and neoplastic intestinal epithelial cells. A clear understanding of the factors responsible for regulation of normal and abnormal intestinal cell growth will greatly facilitate the development of therapeutic strategies for the prevention and treatment of gastrointestinal cancers.