To correlate the magnetic resonance (MR) imaging characteristics of exofocal postischemic neuronal death (EPND) in the substantia nigra (SN) with associated histologic changes, we occluded the left middle cerebral artery of rats for 1, 4, 7, or 12 days. Day 1 (post-occlusion) T(2)-weighted images revealed high signal intensity indicative of infarction in the ipsilateral caudate nucleus, putamen, and cortex but not the SN. Diffusion-weighted images (DWIs) on day 1 similarly failed to reveal any changes in the SN. However, on day 4, DWIs revealed high signal intensity in the ipsilateral SN, in which the apparent diffusion coefficient (ADC) transiently decreased (P<0.05) while the T(2)-value increased (P<0.05). These measures returned to and remained at control levels on days 7 and 12. Histologic examination on day 4 revealed dark-staining neurons, markedly swollen perivascular astrocytic end-feet, many swollen neurons with cytoplasmic microvacuoles that mainly originated in the rough endoplasmic reticulum, and strongly roughed neuropils. Reactive astrocytes and dark neurons most frequently appeared on days 7 and 12. The severity of cellular swelling paralleled the change in the ADC. These results demonstrate that a transient high-intensity signal on DWIs, indicative of a decrease in the ADC, is predictive of EPND in the SN.