One-hundred and twenty 6-week-old 257BL/65 mice were fed for 2 or 7 weeks with diets supplemented with different combinations of bile acids and calcium. The effect of calcium, bile acids and the duration of these treatments on proliferative indices of the colonic mucosa was studied with a multiway analysis of variance. In mice not treated with bile acids, a low level (0.1%) of calcium in the diet was related to a significantly higher number of cells in each compartment of the crypt, compared with diets supplemented with 0.5 and 1% calcium (P < 0.01). There was no difference between the groups fed with normal and high calcium diets. Bile acids significantly increased proliferative indices in all animal groups whatever the duration of the treatment; however, this effect was significantly lower in the mice fed with 0.5% and 1% calcium than in those fed with 0.1% calcium (P < 0.01). There was a significant interaction between the effect of bile acids and the effect of calcium regarding the number of labeled cells and the labeling indices. Duration of the treatment had little effect on these indices. The effect of bile acids on colonic proliferative activity could be significantly reduced by calcium supplementation, and this effect was stable with time. Although there was no toxic effect of the highest calcium diet, there was no advantage in increasing the calcium dose beyond 0.5%.