It has been suggested that calcium and cadmium compete for an intestinal transport system that is vitamin D dependent. To further test this hypothesis, the interaction between calcium and cadmium during transport in the duodenum of rat was investigated. Control rats maintained on a diet adequate in vitamin D, calcium, and phosphorus were compared to rats on the same diet administered 500 ng of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 4 hr before transport measurement with everted sacs. Active transport of calcium was evident in control rats and was further stimulated by exogenous 1,25(OH)2D3. Added to mucosal bathing fluid 10 micron cadmium partially inhibited active calcium transport both in controls and in rats receiving 1,25(OH)2D3; 100 microM cadmium completely blocked active transport in both groups. Water transport was also inhibited by 10 and 100 microM cadmium. Cadmium uptake and transport were not affected by 1,25(OH)2D3. The accumulation of cadmium in mucosal tissue was significantly inhibited by 1 mM calcium, but there was no significant effect on uptake or transmural transport. The findings suggest that cadmium and calcium do not interact specifically at a 1,25(OH)2D3-dependent transport site. The interaction between calcium and cadmium in the duodenal mucosa could be related to the action of cadmium in blocking active transport processes.