A pharmacokinetic study with high doses of frusemide was performed in 9 patients with acute tubulopathy, treated by hemodialysis. The patients were studied between 6-28 days after the beginning of the disease. Renal function was normal before the episode of acute renal shutdown. The diuretic effect of frusemide was closely related to creatinine clearance (Ccr): no effect in anuric cases, moderate effect if Ccr was lower than 10 ml/min, marked effect if Ccr was higher than 10 ml/min. A good correlation was found between the natriuretic effect and the renal elimination of frusemide; however, no direct relationship could be demonstrated between drug plasma level and natriuresis. Frusemide half-life in plasma was short even in anuric patients, suggesting the existence of an extra renal excretion and/or inactivation pathway. Hence toxic side effects due to drug accumulation should not appear in the recommended 1 g/day regimen.