The effects of renal function on human renal fluoride (F-) excretion and serum F- concentrations were studied in subjects with normal renal function, in patients with variable degrees of renal insufficiency and in patients undergoing regular hemodialysis treatment. The mechanisms of human renal F- excretion include glomerular filtration and tubular reabsorption. Patients suffering from chronic renal disease tend to continue to excrete normal dietary loads of F- until the creatinine clearance decreases below 25 ml/min. In chronic renal failure elevation of the serum fluoride concentration is delayed and less than might be expected from impairment of the glomerular filtration rate, because tubular reabsorption diminishes presumably due to expansion of the extracellular fluid compartiment.