The histologic description of cerebral ischemia is complex, and within most lesions there are regional variations in degrees of neuronal cell injury, edema, and neuropil disruption. These parameters of tissue injury were analyzed histopathologically in transient and permanent experimental cerebral ischemia in 15 rabbits and the results were spatially correlated with MR images of pre- and postmortem (formalin-fixed) brains. MR was performed at 1.5 T (eight animals) and at 0.38 T (seven animals). Areas of high signal on T2-weighted MR images were closely correlated with histologic signs of cytotoxic glial edema and with disruption of the neuropil (widening of the interstitial spaces in the background matrix of glial and neuronal cellular processes), but MR tended to underestimate the extent of ischemic neuronal injury, especially low-grade histologic changes (mild neuronal shrinkage and nuclear basophilia). Low-grade ischemic neuronal changes were often found in the penumbra zone of ischemic lesions in areas that appeared normal on T2-weighted MR. High-grade neuronal injury was also seen occasionally in areas of normal signal on MR, especially in the striatum. No significant differences were seen on T2-weighted MR between the experimental groups with respect to transient vs permanent occlusion, in vivo vs in vitro MR, and low vs high magnetic field. In the setting of suspected acute cerebral ischemia, an abnormal T2-weighted MR study often underestimates the extent of neuronal ischemic injury, especially potentially reversible injury; and a normal MR study does not completely exclude significant neuronal ischemic injury.