The basic pathogenetic defect in patients with Bartter's syndrome remains unknown, although the possibility that a defect in membrane ion transport underlies the syndrome has been explored by several investigators. The purpose of the present study was to investigate abnormalities in erythrocyte sodium transport in five patients with Bartter's syndrome and to examine the effect of treatment with prostaglandin synthetase inhibitors on these abnormalities.In five patients with Bartter's syndrome, the rate of passive sodium leak from the erythrocyte was 1.04 ± 0.21 mmoles of sodium per liter of erythrocytes per hr, compared to 0.39 ± 0.06 mmoles of sodium per liter of erythrocytes per hr in controls (P< 0.025). Treatment with prostaglandin synthetase inhibitors had little effect on this erythrocyte sodium transport abnormality. After treatment with either acetylsalicylic acid at a dosage of 50 mg/kg/day or indomethacin at a dosage of 100 mg/day, the rate of passive sodium leak averaged 0.96 ± 0.10 mmoles of sodium per liter of erythrocytes per hr in the patients with Bartter's syndrome.In vitrothere was no significant effect of prostaglandin E2on erythrocyte sodium transport, nor did a lowered potassium concentrationin vitroreproduce the changes in sodium transport which we had noted in patients with Bartter's syndrome.We would conclude that one of the basic abnormalities in patients with Bartter's syndrome is a disorder in electrolyte transport at the level of the cell membrane. Prostaglandin synthetase inhibitors have been demonstrated to reverse many of the secondary manifestations of Bartter's syndrome, but they did not seem to affect the membrane transport defect.SpeculationThe most basic defect described to date in patients with Bartter's syndrome may be an abnormality in electrolyte transport at the level of the cell membrane. The abnormality does not appear to be altered by treatment with prostaglandin synthetase inhibitors; perhaps this explains the failure of these agents to totally correct the clinical syndrome.