The aim of this study was to determine the ability of disodium dichloromethylene diphosphonate (Cl2MDP) to reduce the hypercalcemia secondary to skeletal metastases and induced by stimulation of bone resorption by malignant cells. Five patients with hypercalcemia due to bone metastases of breast or renal cancer were treated orally for 4 wk with 3,200 mg of Cl2MDP and 4 wk with a placebo in a double blind, crossover study. During the Cl2MDP period of administration four patients experienced a rapid and significant decrease in serum calcium and urinary calcium excretion together with an increase in alkaline phosphatase. In the remaining patient who developed a sudden paraplegia at the onset of the therapy followed by a marked increase in serum calcium levels and urinary calcium excretion, Cl2MDP was able to reverse this worsening of hypercalcemia or to reduce serum and urinary calcium to normal values. For all patients, urinary hydroxyproline excretion was unchanged during the Cl2MDP period when compared with the prestudy or placebo periods. From these results, and because of the rapid relapse of hypercalcemia during the placebo period or after withdrawal of the treatment, we can conclude that Cl2MDP is capable of reducing excessive mobilization of calcium resulting from bone metastases.