BACKGROUND Disorders in sodium metabolism such as an increased total body exchangeable sodium, were found in diabetic patients, although the underlying mechanisms were not clear. The aim of the study was to evaluate red blood cell sodium transport in patients with insulin dependent diabetes mellitus (IDDM) without diabetic nephropathy. RESULTS Renal hemodynamics using the clearance of inulin and para-amino-hippuric acid during euglycemic clamp and red blood cell sodium transport were examined in 13 IDDM patients without microalbuminuria and in 12 weight-, age- and sex-matched healthy controls. Despite normal renal hemodynamics and intracellular sodium concentrations (6.57 +/- 1.45 vs 5.95 +/- 0.60 mmol/l), IDDM patients had lowered clearance of sodium (2.22 +/_ 1.11 vs 3.24 +/- 1.32 ml/min; p < 0.01) and increased activity of natrium-lithium countertransport compared to C (0.76 +/- 0.50 vs 0.31 +/- 0.22 mmol.l-1 .h-1; p < 0.01). No significant differences between IDDM and C were found in Na+-K+ pump (7.95 +/- 1.95 vs 6.9 +/- 0.99 mmol.l-1 .h-1), in Na+-K+ cotransport (0.68 +/- 0.82 vs 0.82 +/- 0.71 mmol.l-1 .h-1) and in passive Na+ permeability (0.11 +/- 0.05 vs 0.09 +/- 0.02 mmoll.l-1 .h-1). CONCLUSIONS IDDM patients without signs of diabetic nephropathy have shown changes in sodium-lithium countertransport which could play a role in the pathogenesis of diabetic nephropathy and hypertension in the course of the disease.