Six patients with symptomatic osseous Paget's disease were treated with a four-day course of mithramycin (25µg/kg/day). The effects of treatment on the plasma calcium, phosphorus, parathyroid hormone, and the urinary fractional clearance of calcium and phosphorus were studied. Mithramycin produced significant hypocalcemia and hypophosphatemia, and also significantly and simultaneously increased the plasma parathyroid hormone concentration. Despite the increase in parathyroid hormone, the hypocalcemia persisted because of the probable blocking effect which mithramycin exerted on the osteoclasts. The physiological response of the kidney to the elevated plasma parathyroid hormone appeared to be well preserved, as evidenced by the decreased fractional excretion of calcium and the increased fractional excretion of phosphorus in the urine; however, the fall in the clearance of calcium could be the result of the decreased filtered load.