The effect of magnesium deficiency on the response to parathyroid hormone has been investigated in vitro and in vivo. Parathyroid hormone increased the release of calcium, inorganic phosphate and hydroxyproline from rat femora into the incubation medium, but had a lesser effect on bones from magnesium-deficient animals than on femora from control rats. Similarly, injection of the hormone into thyro-parathyroidectomized rats produced smaller rises in plasma calcium and magnesium concentrations in magnesium-deficient rats than in control animals. It is concluded that magnesium deficiency inhibits the action of parathyroid hormone on its target organs.