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Background-Increased dietary calcium might reduce colorectal cancer risk, possibly by reduction of colonic epithelial hyperproliferation, but not all studies have demonstrated this. Little is known about the eVects of calcium on colonic apoptosis. Aim-To quantify the eVects of increasing calcium on apoptosis and cell proliferation in normal murine colonic crypt epithelium. Methods-Twenty one day old male C57Bl/6 mice were fed either control AIN-76 diet (0.5% calcium wt/wt; n = 10) or the same supplemented with calcium carbonate (1.0% calcium; n = 10) for 12 weeks. Apoptotic cells in proximal and distal segments were counted and expressed as an apoptotic index (AI: frequency of apoptosis/100 longitudinal crypts). The bromodeoxyuridine (BrdU) labelling index was also determined. DiVerences were analysed by the student's t test. Results-In control animals, the AI was significantly higher in the caecum/ proximal colon (mean, 28.6; SEM, 2.0) compared with the distal colon (mean, 19.9; SEM, 1.8; p = 0.004). In the calcium treated group, the AI in the caecum/ proximal colon (mean, 30.6; SEM, 1.7) was similar to controls (p = 0.71) but the AI in the distal colon was significantly greater (mean, 32.6; SEM, 1.8; p = 0.001) than in control mice and was raised to values similar to those in the proximal colon. Calcium was also associated with reduced crypt cellularity and, in the proximal colon, a downward shift in the crypt position at which apoptosis occurred. There were no significant diVerences in the BrdU labelling index between groups or between proximal and distal colonic segments in each group. Conclusions-Increased dietary calcium is associated with the induction of apoptosis in normal mouse distal colonic epithelium without aVecting cell proliferation. This might contribute to its putative chemopreventive role in colorectal carcinogenesis. Whether this eVect is direct or indirect requires further study. (J Clin Pathol 2000;53:302-307)