BACKGROUNDBecause studies of diet and colorectal carcinoma tend to be large and complex, researchers have long been interested in the investigation of dietary exposures in relation to putative intermediate markers of large bowel malignancy, such as colorectal epithelial cell proliferation. The basic hypothesis underlying these investigations is that specific dietary components may reduce or increase the rate of cell proliferation, which, in turn, may reduce or increase neoplastic changes in the large bowel.METHODSThe authors assessed the effects of a 4‐year, low‐fat, high‐fiber, fruit and vegetable‐enriched dietary intervention on colorectal epithelial cell proliferation among 399 participants from the Polyp Prevention Trial, a randomized multicenter trial with adenoma recurrence as the primary endpoint. Rectal biopsies were taken from flat, normal appearing mucosa on patients at baseline, after 1 year, and after 4 years. Two assays, bromodeoxyuridine (Brd U) and proliferating cell nuclear antigen (PCNA), were used to evaluate two summary measures of proliferation: the labeling index (LI) and the proliferative height (PH).RESULTSThere were no significant differences between changes in LI and PH over the 4‐year period for the intervention and control groups. This finding parallels the finding in the larger primary study, in which the dietary intervention did not alter adenoma recurrence rates.CONCLUSIONSA low‐fat, high‐fiber, fruit and vegetable‐enriched dietary intervention did not alter rectal mucosal cell proliferation rates. Cancer 2003;98:1161–8. Published 2003 by the American Cancer Society.DOI 10.1002/cncr.11608