The possibility that aescin might have a nephrotoxic side effect has been investigated by clearance studies in kidneys of healthy rats and by toleration studies in rats with damaged kidneys. The effect of aescin, both free and albumin-bound, on renal tubular transport processes was studied in the model of the isolated, artificially perfused frog kidney. The rates at which different concentrations of aescin were bound to rat plasma proteins were determined in vitro. The clearance of i.v. aescin was 13% of creatinine clearance and 7% of p-aminohippurate (PAH) clearance; this rules out the tubular secretion of aescin. No deaths occurred among aminonucleoside-damaged rats given i.v. sodium aescinate 2.2 mg/kg, but rats damaged with mercuric chloride or uranyl nitrate had exactly the same mortality rate as those given 2.2 mg/kg i.v. of sodium aescinate alone. The rats received four injections in all of aescin 0.35 mg/kg i.v., given at intervals of two days. Aescin had no effect on renal damage caused by aminonucleoside, mercuric chloride or uranyl nitrate. Aescin concentrations of 0.2 mg/l and 2.0 mg/l in the perfusion fluid increased the excretion of Na+ and glucose by the frog kidney and reduced the reabsorption of both these substances. With a sodium aescinate concentration of 5 mg/l the production of urine ceased. When 1% (w/v) of albumin was added to the perfusion fluid, even sodium aescinate 5 mg/l had no effect on the tubular transport of Na+, glucose and water. The fact that about 50% of aescin was not bound to plasma protein in vitro suggests that some of the small amount of aescin in the glomerular filtrate is reabsorbed in the tubules.