MRI studies using mouse brain models of ischemia are becoming a valuable tool for understanding the mechanism of stroke, since transgenic models are now available. However, the small size of the mouse brain and the surgical complexity of creating ischemia in mice make it technically challenging to obtain high-quality MRI data. Therefore, there are few reports of MRI studies in murine cerebral ischemia. In this project a newly developed rapid 3D diffusion-weighted imaging (DWI) technique was applied to study experimental stroke in a mouse model of reversible middle cerebral artery occlusion (MCAO). Ischemic volumes were successfully delineated using this 3D whole-brain imaging technique with high spatial (0.34 × 0.5 × 1.0 mm3 before zero-filling) and temporal (7 min) resolution. The 3D observation revealed the characteristic evolution of stroke after transient MCAO. There was a temporarily high diffusion constant in the cortex during early reperfusion, followed by a secondary energy failure in the cortex and caudate-putamen at 6 and 21 h of reperfusion. Magn Reson Med 46:183–188, 2001. © 2001 Wiley-Liss, Inc.