Cerebral ischemia induces transcriptional changes in a number of pathophysiologically important genes. Here we have systematically studied gene expression changes in the cortex after 150 min of focal cortical ischemia and 2 and 6 h reperfusion in the mouse by a fragment display technique (restriction-mediated differential display, RMDD). We identified 57 transcriptionally altered genes, of which 46 were known genes, and 11 unknown sequences. Of note, 14% of the regulated genes detected at 2 h reperfusion time were co-regulated in the contralateral cortex. Four genes were verified to be upregulated by quantitative PCR. These were Metallothionein-II (mt2), Receptor (calcitonin)-activity modifying protein 2 (ramp2), Mitochondrial phosphoprotein 65 (MIPP65), and the transcription elongation factor B2/elongin B (tceb). We could identify several genes that are known to be induced by cerebral ischemia, such as the metallothioneins and c-fos. Many of the genes identified provide hints to potential new mechanisms in ischemic pathophysiology. We discuss the identity of the regulated genes in view of their possible usefulness for pharmacological intervention in cerebral ischemia.