Increased GFR and decreased renal vascular resistance are common renal hemodynamic changes in persons with early, uncomplicated, insulin-dependent diabetes mellitus. It has been hypothesized that excess total-body sodium in patients with diabetes contributes to the renal vasodilation, possibly by suppressing vasoconstricting neurohormonal systems. This study was undertaken to examine whether sodium restriction could normalize these renal abnormalities. Subjects were 12 male patients with uncomplicated insulin-dependent diabetes mellitus (duration, < 5 yr). Results were compared with those of an age- and gender-matched control group. All subjects received either a high-sodium diet (200 mmol/day) or a sodium-restricted diet (20 mmol/day) for 7 days, according to a randomized crossover protocol. GFR and RPF were measured using inulin and para-aminohippurate clearance techniques, respectively. Subjects with diabetes were maintained euglycemic during the clearance measurements. GFR was significantly higher in the diabetic group than in the control group with sodium repletion (124 +/- 4 versus 107 +/- 8 mL/min/1.73 m2; P = 0.03), and renal vascular resistance was significantly reduced (94 +/- 6 versus 107 +/- 17 mm Hg/L/min; P = 0.05). In response to sodium restriction, the hematocrit increased significantly in both groups, as did PRA and aldosterone, although responses in the diabetic group were somewhat blunted, indicating persisting volume expansion. Despite this humoral activation, sodium restriction had little effect on renal hemodynamic function in control subjects. In the diabetic subjects, this maneuver appeared to exacerbate the underlying renal abnormalities, with the GFR increasing to 131 +/- 4 mL/min/1.73 m2 (P = 0.05) and the renal vascular resistance declining to 73 +/- 5 mm Hg/L/min (P = 0.001). These data indicate that, rather than correcting renal hyperperfusion, sodium restriction exacerbates these characteristic abnormalities, suggesting that mechanisms other than suppression of vasoconstrictor activity are operative in the underlying renal hemodynamic abnormalities of early, uncomplicated, insulin-dependent diabetes mellitus.