The right middle cerebral artery (MCA) was occluded in cats; after subsequent craniectomy cortical blood flow (CBF) was measured bilaterally with Kr-85, and photographs of the superficial mierovasculature were made. Ventilation was controlled, and Pa-CO2 was altered by changing the concentration of CO2 in the inspired air. In nonischemic cortex CBF varied as an exponential function of Pa-CO2, and the caliber of superficial arterial vessels (50 to 200 mu in diameter) increased with increasing Pa-CO2. In ischemic cortex, changes of Pa-CO2 produced 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 Pa-CO2 produced 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 Pa-CO2 was found in four, and appropriate changes of vessel caliber were found in ail eight. The ischemia-induced impairment of the reactivity of cortical vessels to changes of Pa-CO2 casts doubt on the usefulness of CO2, inhalation for the treatment of strokes of humans.