Change of local cerebral blood flow in response to a single cortical spreading depression of Leão was studied in the brain. During a spreading depression, potassium briefly accumulates in the brain extracellular space. The cortical blood flow was normal during the maximal rate of increase of the extracellular potassium concentration. The blood flow doubled during the subsequent period of normalization of potassium and remained high for one minute thereafter. Thus, potassium cannot be the immediate mediator of the blood flow increase.