Tizolemide is a sulphonamide diuretic. The effect on transepithelial Na transport of tizolemide was investigated in isolated frog skin (Rana temporaria). It was found that tizolemide (2-5 mM, serosal side) decreased transepithelial Na transport (measured as short circuit current and as net sodium flux) within 60 min to 25-40% of the control level resulting from reduction of the unidirectional sodium influx. Tizolemide has alkaline properties and is cleared by a tubular transport system which differs from the PAH-excreting system which transports thiazide diuretics. Tizolemide was almost completely absorbed from the gastrointestinal tract. The drug was mainly eliminated via tubular secretion. Renal clearance of the drug was much lower in patients with compensated cardiac failure than in healthy subjects because of low renal plasma flow. As a consequence, plasma half-life was prolonged considerably in some patients. It was concluded that drugs with mainly tubular renal elimination may have a reduced elimination rate in patients with cardiac diseases despite normal glomerular filtration rate.