Both selenium and calorie restriction are anticarcinogenic in many tumor models, but the mechanisms of action are unknown. This study compared the effects of elevated selenium (Se) intake and calorie restriction on colonic cellular growth. Female weanling rats were divided into four groups: control, 40% calorie restricted, and 4 or 6 mg Se/l H2O as selenate. Control rats and rats given Se consumed the control diet ad libitum. Rats in the 40% calorie-restricted group were pair fed 40% less than the total intake of control rats with a diet designed to provide equal nutrients except calories from carbohydrate. After three weeks, rats were injected with [3H]thymidine (1 muCi/g body wt) and killed one hour later. Se at 4 and 6 mg/l H2O and 40% calorie restriction significantly decreased food intake, weight gain, colon weight, and total colon DNA compared with controls. Total number of cells per crypt was not affected by any treatment, whereas total DNA synthesis was significantly decreased, suggesting that the total number of colonic crypts are reduced by calorie restriction and Se treatment. The rate of cell division was decreased only in rats given 6 mg Se/l H2O. These results indicate that elevated Se intake and caloric restriction decrease colonic mucosal growth by decreasing growth in general, but only very high intakes of Se affect colonic cell turnover.