OBJECTIVE To describe the clinical features, MRI findings, and the pathogenesis of the pure midbrain infarction. METHODS Forty patients with infarcts limited to the midbrain were studied. MRI and angiography (mostly MR angiography) were performed in all patients. RESULTS Clinical manifestations included gait ataxia in 27 (68%) patients, dysarthria in 22 (55%), limb ataxia in 20 (50%), sensory symptoms in 17 (43%), third nerve palsy in 14 (35%), definitive limb weakness (< or =IV/V) in nine (23%), and internuclear ophthalmoplegia in five (13%). According to MRI findings, the lesions were categorized into four groups. The anteromedial group (n = 18) was characterized by oculomotor disturbances (89%), ataxia (89%, bilateral in 17%), and sensory changes (39%) usually restricted to the perioral and hand areas. Lesions restricted to the subcortical area (n = 10) were usually related to small vessel disease (SVD) (78%), whereas those involving the medial surface (n = 8) were caused by large vessel disease (LVD) (78%). The anterolateral group (n = 11) was characterized by ataxia (70%) and definitive hemiparesis (30%) usually caused by LVD (82%). The combined group (n = 6) had frequent oculomotor disturbances (83%), definitive hemiparesis (67%), and ataxia (50%) and was usually associated with LVD (67%). The lateral group (n = 2) was characterized by prominent sensory symptoms. The prognosis was generally good except for one patient with a bilateral lesion. CONCLUSIONS Clinical-radiologic correlation study yields four distinct subgroups: anteromedial, anterolateral, combined, and lateral. Large vessel disease and small vessel disease are usual pathogenic mechanisms, whereas cardiogenic embolism is rare.