Mechanisms involved in the hypercalciuria caused by high levels of protein intake were investigated. Six healthy males participated in a 20-day metabolic study. During the first 10-day period, all subjects were given a 47 g protein diet and during the second 10-day period, a 142 g protein diet. Calcium, magnesium and phosphorus intakes were kept constant at 515, 320 and 1,110 mg daily, respectively. Urinary calcium was elevated significantly when the protein intake was increased. Glomerular filtration rate and calcium clearance were increased significantly when the high protein diet was fed; the fractional tubular reabsorption of calcium was decreased from 98.4 to 97.4%. Thus, the increase in urinary calcium caused by the high protein diet appears to be due in part to an increase in the filtered load of calcium by the glomeruli and in part to a decrease in calcium reabsorption by the renal tubules. The level of protein intake had no effect on the fasting serum concentrations of parathyroid hormone, total calcium, magnesium or inorganic phosphorus or plasma ultrafiltrable calcium.