To evaluate the influence of glucose (one of the non-creatinine chromogens) on measurement of creatinine clearance (Ccr), Ccr measured by Owen's method, which eliminates the influence of glucose, was compared with values obtained by the standard Peters' method in 118 NIDDM patients. Serum and urine creatinine concentrations measured by Peters' method increased with increasing glucose concentration when compared with Owen's method. Serum creatinine measurment was even more markedly affected than urinary creatinine. Consequently, Ccr measured by Peters' method decreased with increasing plasma glucose concentration when compared with Owen's method, and was only 74 m//min on average in non-albuminuric (AER<15 μg/min) cases, in which Ccr measured by Owen's method was 101 ml/min. Ccr determined by Owen's method in microalbuminuric (15-150 μg/min) cases was significantly higher (p<0.05) than in non-albuminuric cases. With Owen's method, elevated Ccr was seen more frequently in cases with a duration of diabetes less than 10 years. In conclusion, Owen's method seems to be preferable to Peters' method for the detection of renal hyperfunction in early diabetic nephropathy in NIDDM patients.