Renal toxicity following a single iv nonlethal dose (6 mg/kg) of cisplatin (CDDP) was investigated in male F344 rats pretreated with 20 mg/kg of acetazolamide (ACZ) sc 30 minutes before CDDP administration. There was a decrease in nephrotoxicity as indicated by a smaller elevation of BUN, a milder histopathologic lesion, and a more rapid recovery of BUN in ACZ-pretreated animals. Renal platinum content of rats receiving ACZ was significantly lower than that in animals treated with CDDP alone. There was no change in platinum level in the plasma or the liver but there was a decreased platinum excretion in urine during 24 hours after treatment. Reduction of platinum concentration in the kidney might account for protection against the renal toxicity. The diuretic ACZ might be useful in the hydration regimens used clinically to prevent renal toxicity from CDDP.