To evaluate the glomerulo-tubular balance of sodium and water in the proximal tubules of diabetic patients with elevated glomerular filtration rate, the renal plasma clearance of lithium and the glomerular filtration rate (51Cr-EDTA plasma clearance) were determined simultaneously in 11 ambulatory Type 1 (insulin-dependent) diabetic patients (aged 25-35 years) with no evidence of diabetic nephropathy and in 10 age-matched healthy subjects. The renal plasma clearance of lithium, which is a measure of flow from the proximal tubule into the thin descending limb of the loop of Henle, did not differ between diabetic and control subjects (28.9 +/- 4.0 versus 28.3 +/- 5.1 ml/min per 1.73 m2 surface area, mean +/- SD), whereas the glomerular filtration rate in the diabetic patients was significantly higher than in the control subjects (136 +/- 10.2 versus 108 +/- 13.6 ml/min per 1.73 m2, p less than 0.001). The same held true for the fractional reabsorption rate in the proximal tubules (78.7 +/- 3.2 versus 73.6 +/- 4.9%, p less than 0.02). The results indicate that the elevation of the glomerular filtration rate in diabetic patients is associated with a parallel increase in the proximal reabsorption rate. This type of glomerulo-tubular balance implies that the flow of water and flux of sodium to the segments distal to the proximal tubule are kept constant during variations in the glomerular filtration rate.