The authors investigated the protective effects of the urinary trypsin inhibitor urinastatin on acute renal failure induced in rats by gentamicin (240 mg/kg body weight i.p. for 3 days) and by mercuric chloride (3 mg/kg s.c.). In rats injected with gentamicin, glomerular filtration rate (GFR), renal plasma flow (RPF), and percent fractional sodium excretion (%FENa) were 151 ± 51 μl/min/100 g body weight, 0.69 ± 0.31 ml/min/100 g and 0.73 ± 0.32, respectively, whereas in rats given 100,000 U of urinastatin the renal function was significantly ameliorated (GFR 318 ± 43 μl/min/100 g RPF 1.41 ± 0.35 ml/min/100 g), although the %FENa (0.46 ± 0.26) was not significantly improved. A 50,000-unit dose of urinastatin prevented the deterioration of renal function to some extent following administration of gentamicin: GFR 219 ± 66 μl/min/100 g and RPF 0.93 ± 0.43 ml/min/100 g. In the study using mercuric chloride, treatment with 75,000 U of urinastatin protected the kidney from HgCl2 poisoning, yielding values of 294 ± 93 μl/min/100 g (GFR), 1.03 ± 0.41 ml/min/100 g (RPF), and 1.44 ± 0.72 μl/min/100 g (%FENa) as compared with respective values of 169 ± 48 μl/min/100 g, 0.7 ± 0.18 ml/min/100 g, and 2.22 ± 1.35 in the untreated rats. Renal histology revealed mild to moderate tubular epithelial changes in untreated rats, but preservation of an almost normal tubular structure in urinastatin-treated rats in both studies.