In order to determine the mechanism of elevated serum inositol in renal failure, the clearance values of inositol and of creatinine were measured in patients with normal kidney function and in those whose renal function was impaired due to varying causes. Mean serum inositol level in controls was 5.6 μg/ml, and in patients with renal failure 28.6 μg/ml. In control patients, inositol clearance was 2.8 ml/min, and tubular reabsorption of inositol was found to be over 97%. The inositol clearance of patients in renal failure varied from 0.62 to 17 ml/min. The ratio inositol clearance/creatinine clearance was elevated in uremic patients. Total amounts of inositol excreted in the urine of uremic patients were consistently higher than those excreted by control patients. The elevated serum inositol levels seen in renal failure were therefore not primarily caused by inability of the diseased kidney to excrete inositol.