Isotopic clearance techniques have been widely used to measure GFR but may give variable results depending on the level of renal function and the technique used. GFR, measured by the technique of plasma disappearance of 99mTc-labeled diethylenetriaminopentacetic acid ([99mTc]DTPA) was compared with simultaneously obtained urinary clearance of [99mTc]DTPA. GFR was also measured by concurrent 24-h clearance of creatinine. Forty-six measurements of GFR were obtained in 12 patients who had no evidence of renal disease. Plasma disappearance was measured from three timed plasma samples collected 60 to 180 min after the bolus injection of 200 microCi of [99mTc]DTPA and was calculated as the product of the volume of distribution (milliliters) at time zero and the clearance rate (per minute) as determined by the regression of the monoexponential plot. Urinary clearance was measured as the average of 3 1-h urinary clearances collected after a water diuresis was established. GFR measured by plasma disappearance was significantly greater (P less than 0.001) than GFR measured simultaneously by urinary clearance. There was a linear correlation between GFR measured by urinary clearance and that measured by plasma clearance (r = 0.994). Plasma clearance exceeded urinary clearance by a constant factor of 1.3 over the range studied (urinary clearance range, 49 to 94 mL/min/1.73 m2). It was concluded that at relatively a normal GFR, the plasma clearance of [99mTc]DTPA consistently overestimates the urinary clearance of [99mTc]DTPA.