Erythrocyte sodium-potassium (Na+/K+) -ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6–16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean±SEM 2,156±110 μmol P/l erythrocyte per hour vs. 3,165±175, P0.07 mmol/mmol versus 0.51±0.06 respectively, P +/K+-ATPase activity increased significantly (2,769±169 μmol P/l erythrocyte per hour vs. 2,156±110 in the control period, P +/Li+ countertransport decreased (268±28 μmol Li/l erythrocyte per hour vs. 328+26 in the control period, P +/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.