The renal clearance of inorganic fluoride was studied in 5/6-nephrectomized and kidney-intact rats in order to evaluate the influence of the extracellular fluid volume status on net tubular fluoride reabsorption. Loss of renal functional mass impaired the ability of the hydropenic uremic rat to excrete fluoride, although tubular reabsorption of fluoride was depressed. Fractional fluoride excretion was closely correlated to urinary flow rate in hydropenic rats; no influence of urinary pH from 5.80 to 6.18 could be demonstrated. Acute, moderate expansion of the extracellular fluid volume by isotonic saline was followed by a significant rise in fractional fluoride excretion in uremic as well as in control rats, indicating that extracellular fluid volume is an important physiological determinant of passive tubular fluoride reabsorption.