Fecal diacylglycerol (DAG) concentrations have been suggested as biomarkers for colonic neoplasia because of their potential to be absorbed in the colon and to stimulate epithelial cell proliferation. The interrelationships among nutrient intake, fecal and mucosal DAG, and colonic proliferative markers have not previously been studied. We designed a pilot study to evaluate the feasibility of evaluating these interrelationships in 12 volunteers who had a history of colonic adenomatous polyposis. Total mucosal DAG concentrations were not related to fecal DAG concentrations, but mucosal DAG correlated inversely with the whole crypt labeling index. Dietary intake did not alter fecal DAG concentrations. However, the percentage of calories from dietary fat correlated positively with the whole crypt labeling index. Fiber and calcium intake showed a positive correlation with the labeling index in the upper 40% of the crypt. The present pilot study failed to demonstrate a correlation between dietary components and fecal and total mucosal DAG. Additional studies relating fecal DAG with mucosal proliferation will require the evaluation of DAG concentrations in subcellular compartments of mucosal cells and/or measurement of fecal DAG fatty acid composition.