The occurrence and severity of ischemic cerebral symptoms after carotid occlusion depends on the interdependency of cerebral collateral blood supply. Only those with the "fittest" collateral capacity survive this process of natural selection. Using the transcranial Doppler method in 55 patients with unilateral carotid occlusion, we tested the dependency of each cerebral hemisphere on the remaining patent carotid artery by digital carotid compression, and in 41 of these patients we also tested the carbon dioxide reactivity in each hemisphere. Both hemispheric dependency and carbon dioxide reactivity were compared to 15 healthy controls. Mean blood flow velocities in the middle cerebral artery were lower on the occluded side than on the patent side (p less than 0.003). When the patent carotid artery was compressed middle cerebral artery blood flow velocities on the occluded side were mainly independent of the patent carotid artery, but on the patent side there was a high degree of dependency (p less than 0.0001). Carbon dioxide reactivity did not differ between the hemispheres, but in hemispheres with total dependency, carbon dioxide reactivity was inversely proportional to the severity of stenosis (r = -0.63). Tests of cerebral collateral reserve in patients with unilateral carotid occlusion evaluated by carotid compression and cerebral carbon dioxide reactivity may discriminate between survivors and potential nonsurvivors before the patent carotid artery occludes.