The pharmacokinetics of the loop diuretic piretanide and its diuretic effects were studied in 6 healthy volunteers, 12 pre-dialysis (GFR 7-28 ml/min) and 10 dialysis patients (c-creat. 1-7 ml/min). Single doses up to 96 mg i.v. and orally were well tolerated and audiometry showed no hearing changes. Pharmacokinetic data showed rapid and almost complete absorption (bioavailability 92%) and a rapid elimination with renal clearance of 50% of the total 200 ml/min in the normals and renal clearance of about 50% of actual GFR in the patients. Extrarenal clearance was the same in normals and patients. The rapid extrarenal elimination reduces the risk of accumulation in renal patients but also reduces the active fraction of the dosage being cleared by the kidneys. Therefore, a high dosage and high plasma levels of piretanide were necessary for diuretic effect in uremic patients. The relation between the urinary piretanide excretion rate and the chloruretic effect was similar in normals and uremic patients; Cl- excretion increased 40 mMol per mg piretanide excreted.