The right middle cerebral artery (MCA) was occluded in cats; after subsequent craniectomy cortical blood flow (CBF) was measured bilaterally with85Kr, and photographs of the superficial microvasculature were made. Ventilation was controlled, and PaCO2was altered by changing the concentration of CO2in the inspired air. In nonischemic cortex CBF varied as an exponential function of PaCO2, and the caliber of superficial arterial vessels (50 to 200 μ in diameter) increased with increasing PaCO2. In ischemic cortex, changes of PaCO2produced no change of CBF in six of ten animals studied within one day of occlusion; in four of these six, there was no change in the caliber of arterial vessels. In the four other animals of this group, there was a paradoxical response (an increase of PaCO2produced a decrease of CBF of ischemic cortex), and in two of these four animals, there also was a paradoxical response of the caliber of arterial vessels. In eight animals allowed to survive 5 to 12 days after MCA occlusion, the arterial vessels of ischemic cortex regained some reactivity: a normal response of CBF to changes of PaCO2was found in four, and appropriate changes of vessel caliber were found in all eight. The ischemia-induced impairment of the reactivity of cortical vessels to changes of PaCO2, casts doubt on the usefulness of CO2inhalation for the treatment of strokes of humans.