To assess the intrinsic insulin secretion in patients with diabetes mellitus, the degree of renalreabsorption of C-peptide was estimated by determining urinary C-peptide clearance/creatinine clearance ratio (CCPR/Ccr), and the corrected value of 24-hour urinary C-peptide excretion (24h-UCPR) by CCPR/Ccr was evaluated.<BR>In 51 diabetic patients (DM) and 6 non-diabetic controls, Ccr and CCPR/Ccr were determined in the early morning after fasting. A couple of days before or after these determinations, 24h-UCPR was also measured, and 24h-UCPR/(CCPR/Ccr-10) was employed as the corrected value of 24h-UCPR (c-24h-UCPR). The value of CCPR/Ccr was 0.10±0.04 (mean±SD) in controls, whereas in DM it showed a wide range from 0.07 to 0.88 (0.27±0.16). CCPR/Ccr was correlated significantly with fasting plasma glucose (r=0.36, p<0.002), but not with HbA₁ (r=0.18) or urinary N-acetyl-β-D-glucosaminidase (r=0.29). In DM with Ccr<70ml/min or with proteinuria, the levels of CCPR/Ccr tended to be slightly higher than those in DM with normal renal function, but with no significant difference. 24h-UCPR values in controls and DM were 56.6±26.4 μg/day and 62.2±35.8μg/day, and c-24h-UCPR values were 58.2±28.1μg/day and 27.9±17.3μg/day, respectively. In DM with Ccr>70ml/min, c-24h-UCPR was correlated more significantly with integrated serum insulin or C-peptide concentrations, compared to 24h-UCPR, before and one and two hours after breakfast. The linear regressions of the increments of serum C-peptide concentrations after breakfast and c-24h-UCPR values were similar in both groups of DM with Ccr>70 ml/min and those with Ccr<70ml/min: in the former it was Y=5.0X+8.4 (r=0.82) and in the latter Y=4.7X+5.5 (r=0.74).<BR>It was revealed that the value of CCPR/Ccr in DM was affected by hyperglycemia and renal dysfunction resulting in higher values, which indicated there was considerable intra-and interpatient variability in urinary C-peptide excretion rates. However, c-24h-UCPR was found to reflect the intrinsic insulin secretion over the whole day more faithfully than 24h-UCPR. Furthermore, c-24h-UCPR was considered valid even in DM with renal dysfunction.