The effect of lowering renal cortical sulfhydryl concentration on development of acute renal failure (ARF) was evaluated in rats receiving HgCl2(15 mg/kg body weight, im). Within 90 min after HgCl2injection urine flow rate and fractional excretion of sodium (FENa) were significantly elevated above control levels, and they remained elevated throughout the 3‐h experimental period. Urine flow rate and FENawere not significantly elevated above control levels in animals injected with diethyl maléate (3 mmol/kg, ip) 30 min before and 90 min after HgCl2(DEM/HgCl2). Administration of DEM alone did not alter renal function. Although lower than control levels, concentrations of protein‐bound sulfhydryl groups (PBSH) were comparable in HgCl2‐ and DEM/HgCl2‐treated animals. In contrast, concentrations of nonprotein sulfhydryl groups (NPSH) were 62% lower in DEM/HgCl2animals than in those treated with HgCl2alone. Similarly, Hg accumulation was 54% lower in DEM/HgCl2‐treated animals than in animals treated with HgCl2alone. These results suggest that NPSH play an Important role in Hg uptake and subsequent development of Hg toxicity.