Proliferative abnormalities of the normal colorectal mucosa have been proposed as a possible marker of enhanced susceptibility to colorectal cancer. A case-control study was conducted to compare the cell kinetics of normal colon mucosa through the different steps of the adenoma-carcinoma sequence. The number and position of labelled epithelial nuclei afterin vitroincubation of tritiated thymidine were compared in patients with large bowel cancer (n= 39), large adenoma ≥1 cm (n= 47), small adenoma (n= 30) and in controls (n= 135). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), comparing the second fertile (OR2) and the third tertile (OR3) to the first one. There was no significant difference in the overall cell proliferation rate when comparing cancer, large adenoma and small adenoma groups to the control group. The ratio number of labelled cells in the upper 40% of the crypt/total number of labelled cells (index) was found to be significantly higher only when the cancer group was compared to the control group: OR2= 5.87 (1.33–25.90), OR3= 9.48 (2.07–43.38),Pfor trend = 0.002. The upward shift of the proliferative compartment in the normal mucosa of patients with large bowel cancer suggests that this abnormality is related to cancer risk.