Background and Purpose-Lacunar infarction accounts for 25% of ischemic strokes, but the pathological characteristics have not been investigated systematically. A new experimental model of lacunar infarction in the miniature pig was developed to investigate the pathophysiological changes in the corticospinal tract from the acute to chronic phases. Methods-Thirty-five miniature pigs underwent transcranial surgery for permanent anterior choroidal artery occlusion. Animals recovered for 24 hours (n = 7), 2 (n = 5), 3 (n = 2), 4 (n = 2), 6 (n = 1), 7 (n = 7), 8 (n = 2), and 9 days (n = 1), 2 weeks (n = 2), 4 weeks (n = 3), and more than 4 weeks (n = 3). Neurology, electrophysiology, histology, and MRI were performed. Seven additional miniature pigs underwent transient anterior choroidal artery occlusion to study muscle motor-evoked potentials and evaluate corticospinal tract function during transient anterior choroidal artery occlusion. Results-The protocol had a 91.4% success rate in induction of internal capsule infarction 286 +/- 153 mm(3) ( mean +/- SD). Motor-evoked potentials revealed the presence of penumbral tissue in the internal capsule after 6 to 15 minutes anterior choroidal artery occlusion. Total neurological deficit scores of 15.0 (95% CI, 13.5 to 16.4) and 3.4 (0.3 to 6.4) were recorded for permanent anterior choroidal artery occlusion and sham groups, respectively (P < 0.001, maximum score 25) with motor deficit scores of 3.4 (95% CI, 2.9 to 4.0) and 0.0 (CI, 0.0 to 0.0), respectively (P < 0.001, maximum score 9). Histology revealed that the internal capsule lesion expands gradually from acute to chronic phases. Conclusions-This new model of lacunar infarction induces a reproducible infarct in subcortical white matter with a measurable functional deficit and evidence of penumbral tissue acutely.