The effect of brief periods of phosphate administration on indices of human skeletal metabolism was investigated. Thirteen subjects (8 women, 5 men; 19-36 years old) received 2 g of oral phosphate daily for 5 days. Serum phosphorus rose 26% (3.8 +/- 0.1 mg/dl to 4.8 +/- 0.1 mg/dl; p less than .01) while total calcium fell (9.3 +/- 0.1 mg/dl to 8.9 +/- 0.1 mg/dl; p less than .01). Parathyroid hormone levels increased by 50% (14.1 +/- 2.0 pg/ml to 21.5 +/- 1.7 pg/ml; p less than .05) although values remained within the normal range. A persistent phosphaturia (0.64 +/- 0.10 g/g Cr to 1.8 +/- 0.4 g/g Cr; p less than .05) and a 69% fall in urinary calcium (80.8 +/- 10.0 mg/g Cr to 24.6 +/- 6.0 mg/g Cr; p less than .001) were observed. 1,25-dihydroxyvitamin D3 and urinary hydroxyproline concentrations did not change significantly but the bone gamma-carboxyglutamic acid protein (BGP) concentration rose 41% by day 2 (9.6 +/- 1.3 mg/ml to 13.5 +/- 2.2 mg/ml; p less than .005) and remained elevated throughout the study period. These results support the possibility that brief periods of phosphate administration may be useful in the therapy of disorders associated with low bone turnover, such as osteoporosis.