Using a standard protocol (Doppler ultrasonography, electrocardiography, brain computed tomography, and in selected cases angiography, echocardiography, and Holter monitoring) we studied the clinical characteristics and etiological factors in 380 patients with first stroke who had a corresponding infarct limited to the territory of the pial branches of the middle cerebral artery (MCA) on computed tomography. The presumed cause of infarction was large-artery disease (greater than or equal to 50% carotid artery or MCA stenosis or occlusion) in one-third of the patients and cardioembolism in one-fourth of the patients. Half of 230 patients undergoing angiography showed evidence for distal occlusions suggesting artery-to-artery or cardiac emboli. Severe heart disease and potential cardiac sources of embolism were more common in patients with infarcts in the territory of the posterior (inferior) division of MCA than in patients with infarcts in the territory of the anterior (superior) division of MCA. Persisting functional disability on discharge was also more severe in patients with the former than in patients with the latter. The neurological picture was polymorphous and it could sometimes even be misleading, as in some patients with a classical lacunar syndrome or with aphasia and unexpected sparing of speech areas. However, a few clinical syndromes apparently specific for involvement of a single MCA branch could be delineated, and in some instances they were highly predictive of embolism from heart or proximal artery.