The effect of peri-infarct depolarizations on ischaemic injury was studied in rats submitted to 3 h occlusion of the left middle cerebral artery (MCA). The number of depolarizations varied from 1 to 8 and infarct volume from 37 to 159 mm3. The correlation between the two variables revealed a highly significant linear relationship (r = 0.800; p < 0.005), each depolarization accounting for an increase in infarct volume by about 13 mm3. The aggravating effect of repeated depolarizations was also demonstrated by the gradual increase in cortical DC shift duration, in EEG amplitude recovery time, and in EEG delta power with increasing number of depolarizations. Suppression of peri-infarct depolarizations is a rational approach for reducing the severity of ischaemic stroke.