Corn oil (CO), given as a bolus to female C57BL/6J mice, caused a marked increase in cell proliferation in the colon; this was assessed with a two-hour colchicine arrest for mitotic figures (MF) and with [3H]thymidine incorporation for labeled cells (LC) per crypt measured in histological preparations. In contrast, the same amount of fat given as a bolus in a high-fat diet mixture failed to increase cell proliferation. To determine whether a particular component in the diet was responsible for this protective effect, mice were treated with boluses of CO (0.4 ml) mixed with cellulose (CL), starch (ST), sucrose (SU), casein (CS), vitamin mix (VM) or mineral mix (MM). The results indicated that cellulose, starch, and minerals reduced the proliferative activity caused by CO (MF/crypt CO = 1.30 +/- 0.24; CO + CL = 0.55 +/- 0.10, CO + ST = 0.91 +/- 0.23, CO + MM = 0.63 +/- 0.16), whereas sucrose, casein, and vitamin mix did not. To test the implications of these findings in chronic feeding studies, groups of animals were fed (for 4 wks) diets "deficient" in starch and cellulose, calcium, and both the complex carbohydrates and calcium. The results showed that both calcium and complex carbohydrates affected the proliferation rate significantly (for instance, MF/crypt = 1.44 +/- 0.22 for both factors deficient vs. 0.48 +/- 0.05 for both factors present). We concluded that starch, cellulose, and calcium are protective for the toxic effect of CO on the mouse colon.