The purpose of our study was to analyze the effect of cicletanine on kidney function by using clearance and free flow micropuncture techniques in anesthetized rats. In the clearance experiments, cicletanine was tested at three different doses (15, 30 and 60 mg/kg i.v.). The drug dose-dependently increased urine flow, and urinary sodium and chloride excretion. Renal potassium excretion was also significantly enhanced. Cicletanine was as effective as hydrochlorothiazide regarding fractional renal sodium excretion. Mean arterial blood pressure fell after cicletanine at doses of 30 and 60 mg/kg, but at none of the three doses tested did cicletanine affect renal plasma flow and glomerular filtration rate. In this regard it differed from hydrochlorothiazide which was found to markedly decrease glomerular filtration rate at a dose of 10 mg/kg i.v. A coadministration of cicletanine (20 mg/kg i.v.) and hydrochlorothiazide, at a maximal effective dose (20 mg/kg i.v.), induced an additional diuretic and saluretic effect. By puncturing of late proximal, early and late distal nephron segments, an action of cicletanine (30 mg/kg i.v.) in the superficial distal tubule could be established. Thus, cicletanine shares with the thiazide diuretics its tubular site of action despite the disparity in chemical structure between these drugs.