In the present study the effect of mycophenolate mofetil (MMF), an immunosuppressant, on mercuric chloride (HgCl(2))-induced nephrotoxicity in male Wistar rats was investigated. Animals (200-250 g) were divided into five groups and were subjected to a 6-day treatment schedule. The first (control) group received only vehicle without any active drug. The second to fifth groups were administered HgCl(2) challenge (single dose of 5 mg/kg, s.c.) on the fourth day. Additionally, the second group received distilled water (DW) on all 6 days and the third group was administered DW the initial 3 days and MMF (10 mg/kg b.i.d. by oral gavage) on days 4-6. The fourth group was given DW the initial 2 days and MMF on days 3-6 and the fifth group received MMF all 6 days. All animals were euthanized on the sixth day. It was found that HgCl(2) administration caused significant nephrotoxicity, as indicated by a rise in serum creatinine, blood urea and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations, histopathological injury and increased oxidative stress (altered malondialdehyde and glutathione levels) as compared to the control group. Administration of MMF significantly ameliorated HgCl(2)-induced nephrotoxicity. The results suggest the potential of MMF in preventing the acute nephrotoxicity of HgCl(2).