One hour urine C-peptide and creatinine clearance rates were determined simultaneously in 25 hospitalized patients with non-insulin-dependent diabetes mellitus (NIDDM) undergoing sulfonylurea and/or diet treatment. The studies had been performed after an overnight fast on the second day of admission and on a day soon before discharge, with intervals of 18.9±7.0 days. Fasting plasma glucose (FPG) and hemoglobin A 1 c (HbA1 c) values decreased significantly at the second examination as compared to the initial values (FPG: 101±20mg/dl vs. 161±47mg/dl, P<0.005; HbA 1 c: 7.3±1.5% vs. 8.4±1.7%, P<0.005). The urine C-peptide clearance rate also decreased significantly after metabolic control (0.75±0.361/hr vs. 1.06±0.541/hr, P<0.005). Meanwhile, the urine creatinine clearance rate tended to decrease, but the difference was not significant (3.69±2.04l/hr vs. 4.87±2.98l/hr) at the second examination. The data suggest that the urine C-peptide clearance rate is susceptible to the effects of the fluctuation of metabolic states in NIDDM patients. In order to use urinary C-peptide for a follow up study of pancreatic B-cell secretion, the changes in C-peptide clearance under various metabolic conditions must be taken into account.