Mineral balance studies were performed to clarify the mechanism of the development of renal calcification and its prevention by dietary fluoride (0.1% as NaF) in KK mice fed a low magnesium (0.04% ) diet. Upon feeding the diet, the product of urinary calcium and phosphorus concentrations showed a 10-fold increase which was due to a marked rise of the urinary phosphorus concentration. The same phenomenon was also observed in ICR mice which did not develop renal calcification. Therefore, the inherited high susceptibility to renal calcification of KK mice was explicable by a lowered threshold level of the product in the crystal formation of calcium phosphate salt. Supplemental fluoride inhibited the rise of the concentration product, which may partly be responsible for the prevention of the development of renal calcification. The action of fluoride was based on a depressed urinary phosphorus excretion and also a dilution of the excreted calcium and phosphorus by a fluoride-induced polyuria. The diuretic action of fluoride was evidenced by an increased urinary volume, sodium excretion and a decreased osmolality. Feeding the low magnesium diet caused a hyperpotassemia without changes in heart potassium. The hyperpotassemia was prevented by a smaller amount of fluoride than that required for the prevention of renal calcification.