In a process called ischemic preconditioning, a brief, sublethal ischemic insult protects tissue from subsequent, more severe injury. There have been no reports of rapidly induced ischemic preconditioning. The authors sought to develop a model of cerebral ischemic preconditioning in the mouse that can be applied to transgenic and knockout animals. They found that brief middle cerebral artery (MCA) occlusion only minutes before a severe ischemic insult can induce protection from that insult. Here the investigators describe a mouse model of preconditioning using intraluminal MCA occlusion as both the conditioning and the test stimulus. One or three 5-minute episodes of ischemia given 30 minutes before MCA occlusion for 1 or 24 hours (permanent occlusion) confer significant protection as assessed by infarct volume measurements 24 hours later.