Measurements of epithelial cell proliferation in the mucosa of the gastrointestinal tract pointed out the existence of cell kinetic abnormalities which can be involved in the first steps of carcinogenesis. In particular, an increase in the cell proliferation rate and an abnormal distribution of proliferating cells were found both in animals exposed to carcinogens and in human subjects at high risk of gastrointestinal cancer. In some diseases which predispose to cancer (i.e., chronic atropic gastritis, hereditary gastrointestinal cancer, sporadic colorectal neoplasia, chronic ulcerative colitis) we observed an expansion of the proliferative compartment even when the mucosa was not affected by morphological abnormalities. This proliferative feature seems to be associated with the presence of defects in cell differentiation. The abnormality is well detected by the histological examination of the proliferative pattern using microautoradiography after incorporation of tritiated thymidine, or using immunohistochemistry after bromodeoxyuridine uptake. The literature, and our own results, indicate that the search for abnormalities of epithelial cell proliferation can be useful in studying the earliest mechanisms leading to gastrointestinal cancer, in detecting subjects at high cancer risk, and for pilot chemoprevention studies using these abnormalities as intermediate biomarkers of gastrointestinal cancer risk.