Tissue response to 1,25(OH)[subscript]2D[subscript]3 action was evaluated by examining vitamin D-dependent VDR, 24-OHase, and CaBP mRNA expressions, 24-OHase activities, and VDR concentrations in kidney and intestine. Of 4 groups of rats, 2 groups were fed an adequate vitamin D (300-600 IU/wk), 1.0-1.2% calcium (Ca) diet, designated NC, and 2 groups were fed an adequate vitamin D, 0.02% Ca diet, designated LC. One group from each diet was treated with excess vitamin D[subscript]3 (75,000 IU/wk). These groups were designated NCT and LCT, respectively;Plasma 1,25(OH)[subscript]2D[subscript]3 concentrations were quantified and used to calculate metabolic clearance rates (MCR) and production rates (PR) of 1,25(OH)[subscript]2D[subscript]3. Plasma 1,25(OH)[subscript]2D[subscript]3 concentration in NCT rats was low to normal compared with that of NC rats. An increase in plasma 1,25(OH)[subscript]2D[subscript]3 concentration was measured in LC rats (5- to 6-fold) over that of NC rats. Plasma 1,25(OH)[subscript]2D[subscript]3 concentration in LCT rats was not significantly increased. Increases in 1,25(OH)[subscript]2D[subscript]3 PR in hypercalcemic NCT rats by 3 fold and in 1,25(OH)[subscript]2D[subscript]3 MCR in hypocalcemic LCT rats by 3.8-fold, indicated induction of extrarenal 1[alpha]-hydroxylase and 24-hydroxylase, respectively;Plasma PTH concentrations were low (~45 pg/ml) in both NC and NCT rats. Dietary Ca restriction of both LC and LCT groups, however, caused a significant (P < 0.01) and proportional increases in PTH concentration. In the kidney, VDR concentration and 24-OHase activity in NCT rats were increased, but these responses were decreased in LC and LCT rats. In similar fashion, the expression of renal VDR, 24-OHase, and CaBP mRNAs were increased in NCT rats and decreased in LC and LCT rats. In the intestine, VDR concentration was increased by NCT treatment, however, 24-OHase activity appeared suppressed. Thyroparathyroidectomy of NCT rats resulted in a 2-fold increase in intestinal 24-OHase activity over that of intact NCT rats, which suggested a potential role of calcitonin in the suppression of intestinal 24-OHase. Furthermore, calcitonin administration to LCT rats resulted in a significant (P < 0.001) decrease in intestinal 24-OHase mRNA expression. The same calcitonin effect was not attributable to kidney;These results demonstrate tissue-specific regulation of 1,25(OH)[subscript]2D[subscript]3 action in rat kidney and intestine. The data also are suggestive of a novel role for calcitonin as a negative modulator of intestinal 24-OHase activity that would potentially block an important inactivation pathway of 1,25(OH)[subscript]2D[subscript]3.