The effect of a deoxycholic acid instillation on colonic epithelium was investigated and compared with the effect of an intervention scheme in which deoxycholic acid (DCA) treated mice received oral supplements of calcium lactate. The morphology of colonic tissue exposed to DCA was markedly affected when compared to that of untreated controls. Inflammation, edema, and necrosis preceded elevated numbers of mitotic figures appearing 24 h to 48 h after DCA treatment. Proliferative activity as measured by tritiated thymidine uptake and autoradiography was increased 2.5-fold in colonic crypts of DCA treated mice. In contrast mice receiving multiple oral supplements of calcium lactate showed minimal tissue necrosis due to DCA administration and the frequency of mitotic events and cellular proliferation activity remained similar to levels seen in untreated controls. Sequestration of bile acids by calcium salts may provide a scheme for inhibiting the untoward effects of bile acids on the colonic epithelium and a mechanism for blocking the reported co-carcinogenic activity of these agents.