Eighteen patients with hypercalcemia of different etiologies were treated with oral or intravenous inorganic phosphate or both. This therapy caused reduction in serum calcium to normal (15 patients) or near normal levels, rise in serum phosphorus, fall in renal calcium clearance, and increase in phosphate clearance. Symptoms related to hypercalcemia were improved. Glomerular filtration rate (GFR) remained stable. In two patients with GFR <12 ml/min, a marked rise in serum phosphorus and fall in serum calcium occurred; and in one patient hypocalcemia and tetany appeared. Microscopic calcium deposits were found in the kidneys of two patients. A direct and significant relation (P <0.001) was found between changes in serum calcium and the molar product of serum calcium × serum phosphorus; this supports the concept that deposition of calcium phosphate salts, probably in bones, is one of mechanisms by which phosphate lowers serum calcium.