Growing male rats were fed a purified diet containing 0.6% Ca (two groups) or 0.1% Ca (two groups) for 8 weeks. One 0.6% Ca group and one 0.1% Ca group received 25 ppm Cd (as CdC12) in the drinking water. Diets were fed on an equalized basis with the 0.1% Ca + Cd group determining the amount of diet fed to the other groups. Water was provided ad libitum. Terminal body weights were not different among the four groups. Packed cell volumes were depressed in the Cd-exposed groups, especially the 0.1% Ca + Cd group. The highest concentrations of Cd were found in the lungs, liver, and kidneys of the 0.1% Ca + Cd group. More Cd was bound to low molecular weight proteins of the intestinal mucosa from the 0.1% Ca + Cd group than the 0.6% Ca + Cd group. Rats fed the 0.1% Ca diet appeared to have a greater capacity to absorb either Ca or Cd than rats fed the 0.6% Ca diet, as shown by an enhanced binding of 45Ca and 115mCd to intestinal calcium-binding protein (CaBP) in the rats fed the low calcium diet. A portion of the mucosal Cd was accounted for as Cd bound to metallothionein. It was concluded, based upon these experiments, that cadmium retention and signs of toxicity are enhanced by feeding low Ca diet and that the increased CaBP activity due to Ca restrictions is responsible for the increased Cd uptake observed.