To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.