This study was designed to test the hypothesis that propofol, which possesses antioxidant properties, would produce greater protection than isoflurane in cerebral ischaemia reperfusion injury, at dose levels that produced similar affects on brain electrical activity. Twenty Sprague-Dawley rats were anaesthetized using isoflurane 1.5% in air/oxygen, and mechanically ventilated to a PaCO2 of 4.5 kPa. Following 90 min of middle cerebral artery occlusion using an intraluminal filament, rats were given, in random order, either propofol 1 mg kg-1 min-1 or isoflurane 3% (both of which have been shown to reliably produce EEG burst suppression). After a further 30 min, reperfusion was induced by withdrawing the filament. Animals were killed following 240 min of reperfusion. Rats in the propofol group showed a 21% reduction in mean hemispheric infarct volume when compared with the isoflurane group (P < 0.0001). These data suggest that propofol may act by mechanisms in addition to CMRO2 depression, and provide a basis for further studies of propofol neuroprotection.