1. Inorganic fluoride concentrations were determined in serum and urine specimens of 24 subjects receiving a standardized low fluoride intake. Serum fluoride was directly correlated with previous intake and appeared to reflect bone fluoride stores.
2. A positive correlation between creatinine and fluoride clearance was found. However, striking reductions in fluoride clearance, which resulted in increases in serum fluoride, were not usually seen until the creatinine clearance was below 25 ml/min.
3. Parathormone produced an increase in serum fluoride and thyrocalcitonin a decrease, probably by their action on bone.
4. Six patients with chronic increased bone resorption had elevated fluoride concentrations. In five, when treatment was successful, serum fluoride fell. Interpretation of the data from this group of patients is complicated by initially low filtration rates associated with hypercalcaemia and hypercalciuria.
5. The sensitivity of the serum fluoride concentration to previous intake, glomerular filtration and the intensity of bone resorption suggests that the human organism exerts no direct homeostatic control over this ion.