Serum ascorbic acid (AA) is reduced in diabetic patients. Aim of this study was 1) to verify whether such a decrease might be due to an altered urinary excretion of AA, and 2) whether this latter was modified in presence of early diabetic nephropathy with microalbuminuria (albumin excretion rate [AER] > 20 micrograms/min) in a group of 21 patients affected by insulin-dependent (type 1) diabetes mellitus (IDDM) as compared with 13 healthy controls matched for sex, age, dietary AA intake, and creatinine clearance per 1.73 m2 (CCl). Mean serum AA (+/- SD) was lower in diabetics (40.3 +/- 14 microM/l) than in controls (85.1 +/- 23.5 microM/l; p = 0.0001) and there was no difference between serum AA of patients with or without microalbuminuria. Urinary excretion of AA to creatinine x 100 (UAA/Cr) was higher in micro- (n = 6; 4.6 +/- 1.7) as compared to normoalbuminurics (n = 15; 1.6 +/- 0.9) or controls (1.5 +/- 1.2; p = 0.0001). For values exceeding renal threshold of tubular AA reabsorption (39 microM) the regression line of serum AA to UAA/Cr was significantly (p = 0.001) steeper in diabetics than in controls, suggesting an impaired tubular reabsorption of filtered AA in IDDM. The ratio of AA clearance to CCl was moreover related to AER (r = 0.48; p = 0.03) and to blood glucose (r = 0.51; p = 0.01), being unrelated to uric acid clearance, glycosuria and to urinary excretion of both alanine aminopeptidase and N-acetyl-beta-glucosaminidase.(ABSTRACT TRUNCATED AT 250 WORDS)