Buckminsterfullerence and its derivatives have recently been shown to exhibit considerable in vivo biological activities. A water-soluble hexasulfonated C₆₀ (FC₄S) has been shown to protect against oxidative stress. Neuroprotective effects of FC₄S were investigated in the present study. Focal cerebral ischemia was produced by a permanent occlusion of the right middle cerebral artery in gerbils. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 24 h after cerebral ischemia. Chronic pretreatment of FC₄S (0.5 and 5.0 mg/kg/day, intraperitoneally for 2 weeks) significantly reduced the infarct volume (by 42% and 68%, respectively) when compared to that of the control group. Results revealed that chronic pretreatment of FC₄S may protect the brain against focal cerebral ischemia.