In order to elucidate if the inhibition mechanisms of Aluminum (Al) on intestinal calcium flux involve some possible action on calbindin-D9k, a series of in vivo and in vitro experiments were carried out in normal and in streptozotocin-induced diabetic male rats. The dose-response curves obtained from the in vitro studies indicate that, in the diabetic group (which has a lower content of calbindin-D9k), the effect of Al on JCa(ms) has a small dependence on rising Al concentration (0-10 microM). The parameters obtained from those curves: Emax (maximum reduction percentage of JCa(ms)) and ED50 (Al concentration that produces half of the highest inhibition) were significantly diminished in this group compared to control. Both s.c. injections of calcitriol (D3) at doses of 0.08 and 0.40 microg/kg body wt. per day and insulin (10 IU/kg body wt. per day), increase the inhibitory effect of Al to levels that did not differ from controls. In vivo gavage of 60 mg/kg body wt. per day of aluminum chloride for 1 week reveals that the degree of reduction of intestinal CaBP9k by Al is directly correlated to duodenal content of this protein (r2 = 0.683, P = 0.022).