Cancer of the large bowel is relatively rare in persons younger than 50 years of age, but its incidence increases sharply in persons older than 60 years of age. We thought that the evaluation of colonic cell proliferation, an accurate biomarker of predisposition to colorectal cancer, might help to elucidate the susceptibility of elderly persons to this common malignancy. Accordingly, 30 persons with normal lower endoscopy results were divided into three age groups (30 to 50,51 to 65, and 66 to 90 years of age; Groups 1, 2, and 3, respectively). Samples of rectal mucosa were taken at endoscopic examination, incubated with [3H]thymidine, and processed with standard autoradiographic techniques. At histologic examination, each intestinal hemicrypt was divided into five equal longitudinal compartments from the fundus (compartment 1) to the surface (compartment 5). The number and the position of labeled cells along the crypt were recorded. The total labeling index (LI) (the ratio of labeled cells to total cells) was significantly higher in Group 3 than in the two other groups. Similarly, the LI per crypt compartment in the most superficial portions of the crypts was consistently higher in persons older than 65 years of age (P less than 0.01 at least), indicating an expansion of the proliferative zone to the most superficial portion of the colonic glands. When the proliferative profiles of the three groups of subjects investigated were compared with those of patients with polyps, an almost complete overlap of values was observed between this population at increased risk for cancer and the subjects in Group 3. We conclude that aging is characterized by an overall increase of epithelial cell proliferation in colorectal mucosa and by an upwards expansion of the proliferative compartment, similar to that observed in a population at risk for cancer of the large bowel.