Acute renal failure (ARF) is a major complication of gentamicin (GM) treatment, which is effective against gram-negative infections. Since experimental evidence suggests a role of reactive oxygen species (ROS) in GM-induced ARF, in this work we studied the effect of a garlic-derived compound, S-allylcysteine (SAC), which is a free radical scavenger, on GM-induced nephrotoxicity. In rats treated with GM (70 mg/kg/12 h/4 days/s.c.), ARF was evident by the: (i) decrease in creatinine clearance and increase in blood urea nitrogen, (ii) decrease in blood glutathione peroxidase (GPx) activity and increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (iii) necrosis of proximal tubular cells. These alterations were prevented by SAC treatment (250 mg/kg/i.p. 24 h before the first dose of GM and 125 mg/kg/12 h/4 days along GM-treatment). Furthermore, SAC prevented the GM-induced oxidative stress (protein carbonyl groups) and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities in renal cortex. In conclusion, SAC ameliorates the GM-induced ARF by a mechanism related, at least in part, to its ability to decrease oxidative stress and to preserve antioxidant enzymes activity in renal cortex.