The cerebral tissue responses to ischemia are modified by many factors, including the mechanism by which ischemia is induced, and the severity and duration. Children can withstand brain ischemic insults that are usually lethal to older patients. Other modifying factors of ischemia, such as barbiturates and serum glucose, remain poorly defined in humans. Once a cerebral ischemic event occurs, for example, after cardiac arrest and resuscitation, secondary events (such as alterations in the perfusability and reactivity of the microcirculation) may aggravate the original ischemic injury at discrete sites of the brain. A more exact definition of a) the limits of reversibility of ischemic injury, b) the histologic features of sublethally injured tissues, and c) the effects of various therapeutic interventions, awaits the development of relatively inexpensive and reproducible animal models of ischemia in which objective comparisons can be made between the nature of the local circulatory conditions and the accompanying histologic abnormalities.