Tissue activity levels of ornithine decarboxylase (ODC) have been suggested to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. Supplemental dietary calcium has been hypothesized and reported to suppress colonic epithelial-cell proliferation. We measured sigmoid and rectal mucosal ODC activity levels in 45 healthy, disease-free subjects with strong family histories of colorectal cancer before and after 2 months, during which daily dietary supplementation with calcium carbonate (to provide 600 mg calcium base) was taken. Although the mean ODC activity levels decreased in both sigmoid and rectal specimens, these changes were small in relation to the standard deviation and were not statistically significant. These data suggest that the magnitude of dietary calcium intake does not significantly influence sigmoid-rectal mucosal ODC activity levels and that ODC measurements may not be a useful intermediate endpoint for interventions designed to interrupt the colon carcinogenic sequence.