We have developed a technique for measuring cortical cerebral blood flow in the rat. The technique is based on the original Kety- Schmidt approach, and involves cannulation of the jugular vein, the common carotid artery, the superior sagittal sinus, and, in some cases a femoral artery and vein. The technique has a number of advantages over other approaches. First, it does not require the calculation of the partition coefficient of the radioactive tracer used in the experiments. Second, it is not affected by possible diffusional limitations of the radioactive tracer. Third, it can be used to measure regional blood flow in the awake, unanesthetized animal.