We developed a new model of embolic cerebral ischemia in the rat which provides a reproducible and predictable infarct volume within the territory supplied by the middle cerebral artery (MCA). The MCA was occluded by an embolus in Wistar rats (n = 71). An additional three non-embolized rats were used as a control. Cerebral blood flow (CBF) was measured by means of laser Doppler flowmetry (LDF) and perfusion weighted imaging (PWI) before and after embolization. The evolution of the lesion was monitored by diffusion weighted imaging (DWI). Cerebral vascular perfusion patterns were examined using laser scanning confocal microscopy. Infarct volumes were measured on hematoxylin and eosin (H&E) stained coronal sections. The lodgment of the clot at the origin of the MCA and the ischemic cell damage were examined using light microscopy. Regional CBF in the ipsilateral parietal cortex decreased to 43 +/- 4.1% (P < 0.05) of preischemic levels (n = 10). Confocal microscopic examination revealed a reduction of cerebral plasma perfusion in the ipsilateral MCA territory (n = 6). MRI measurements showed a reduction in CBF and a hyperintensity DWI encompassing the territory supplied by the MCA (n = 4). An embolus was found in all rats at 24 h after embolization. The infarct volume as a percentage of the contralateral hemisphere was 32.5 +/- 3.31% at 24 h (n = 20), 33.0 +/- 3.6% at 48 h (n = 13), and 34.5 +/- 4.74% at 168 h (n = 12) after embolization. This model of embolic focal cerebral ischemia results in ischemic cell damage and provides a reproducible and predictable infarct volume. This model is relevant to thromboembolic stroke in humans and may be useful in documenting the safety and efficacy of fibrinolytic intervention and in investigating therapies complementary to antithrombotic therapy.