Mannitol is widely used to reduce intracranial pressure and is protective against ischemic and nephrotoxic acute renal failure. However, the capacity of this seemingly innocuous agent to produce acute renal failure is not well recognized. We report herein the clinical course of 8 cases of mannitol-induced acute renal failure. In addition, we reviewed all previously reported cases of mannitol-induced renal failure. In the present series, acute oliguric renal failure developed within 3.5 +/- 1.1 (mean +/- SD) days after receiving daily and total mannitol doses of 189 +/- 64 g and 626 +/- 270 g, respectively, over 3.5 +/- 1.5 days. The peak serum creatinine was 5.7 +/- 2.7 mg/dl and peak osmolal gap was 74 +/- 39 mOsm/kg water. Renal tubular epithelial cells containing vacuoles were seen in the urinary sediments of 6 patients. Renal function improved rapidly upon discontinuation of mannitol and/or removal of mannitol by hemodialysis. In those previously reported cases in which the baseline renal function was normal, acute renal failure developed after receiving total mannitol doses of 1171 +/- 376 g. The peak osmolal gap was 107 +/- 17. In contrast, in those with underlying renal compromise, renal function worsened after a total mannitol dose of 295 +/- 143 g. The pathogenesis of mannitol-induced renal failure is not yet established but may be associated with renal vasoconstriction produced by high concentrations of mannitol. This may be averted in clinical practice by monitoring the osmolal gap, rather than serum osmolality alone, when using mannitol infusions for the treatment of intracranial hypertension.