Background: Recent studies indicate that reactive oxygen species are the major culprits behind the renal damage induced by gentamicin, an aminoglycoside antibiotic used to treat serious and life threatening Gram-negative infections. Experimental evidence suggests a protective role of alpha-linolenic acid supplementation against oxidative stress. The aim of the present study was to investigate the possible beneficial role of alpha-linolenic acid against gentamicin induced renal distress. Methods: Male Wistar rats were divided into three groups of eight rats each, with the first group serving as a control. The other groups were treated intraperitoneally with gentamicin 100 mg/kg body weight per day for 10 days ± alpha-linolenic acid and vitamin E (each given as 250 mg/kg body weight per day). Concentrations of creatinine, urea, cholesterol, inorganic phosphate in serum, malondialdehyde and total sulfhydryl levels, and glutathione-S-transferase, superoxide dismutase, and catalase activity in kidney tissues were determined. Results: Administration of gentamicin to rats induced marked renal failure, characterized by a profound increase in serum creatinine, urea, and cholesterol concentrations, accompanied by significant lowering of renal alkaline phosphatase and acid phosphatase activity, an increase in malondialdehyde, a decline in total sulfhydryl levels, and lowered superoxide dismutase, catalase, and glutathione-S-transferase activity. Cotreatment with alpha-linolenic acid produced amelioration in these biochemical indices of nephrotoxicity in serum as well as in tissue. Further histopathological and human studies are necessary to demonstrate the beneficial effects of alpha-linolenic acid in renal disease. Conclusion: Alpha-linolenic acid may represent a nontoxic and effective intervention strategy in gentamicin induced nephrotoxicity. [ABSTRACT FROM AUTHOR]