Mercurials are known to induce morphological and functional modifications in kidney. The protective effect of octylguanidine on the injury induced by Hg(2+) on renal functions was studied. Octylguanidine administered at a dose of 10 mg/kg body weight prevented the damage induced by Hg(2+) administration at a dose of 3 mg/kg body weight. The findings indicate that octylguanidine spared mitochondria from Hg(2+)-poisoning by preserving their ability to retain matrix content, such as accumulated Ca(2+) and pyridine nucleotides. The hydrophobic amine also protected mitochondria from the Hg(2+)-induced loss of the transmembrane potential, and from the oxidative injury of mitochondrial DNA. In addition, octylguanidine maintained renal functions, such as normal values of creatinine clearance and blood urea nitrogen (BUN), and serum creatinine after Hg(2+) administration. It is proposed that octylguanidine protects kidney by inhibiting Hg(2+) uptake to kidney tissue, and in consequence its binding to mitochondrial membrane through a screening phenomenon, in addition to its known action as inhibitor of permeability transition.