We sought to determine the importance of calcium phosphate deposition in the functional deterioration of damaged or diseased kidneys. Using the remnant-kidney model in rats, we found that dietary phosphate restriction prevented proteinuria, renal calcification, histologic changes, functional deterioration and death in uremia. Histologic examination of the remnant kidney in the nonrestricted animals showed calcium and phosphorus deposits in the cortical tubular cells, basement membranes and interstitium. A similar degree and pattern of calcification have been found in preliminary studies of human end-stage kidneys. Our results suggest that the calcification produced by the altered phosphorus metabolism present in the uremic state incites an inflammatory and fibrotic reaction leading to destruction of the remnant kidney. Phosphate restriction prevents this response in the remnant kidney. The potential applicability of these findings to other forms of experimental renal disease and to clinical uremia remains to be explored.