We used serial positron emission tomography (PET) to study the evolution of functional brain activity within 12 weeks after a first subcortical stroke. Six hemiplegic stroke patients and three normal subjects were scanned twice (PET 1 and PET 2) by using passive elbow movements as an activation paradigm. Increases of regional cerebral blood flow comparing passive movements and rest and differences of regional cerebral blood flow between PET 1 and PET 2 in patients and normal subjects were assessed by using statistical parametric mapping. In controls, activation was found in the contralateral sensorimotor cortex, supplementary motor area, and bilaterally in the inferior parietal cortex with no differences between PET 1 and PET 2. In stroke patients, at PET 1, activation was observed in the bilateral inferior parietal cortex, contralateral sensorimotor cortex, and ipsilateral dorsolateral prefrontal cortex, supplementary motor area, and cingulate cortex. At PET 2, significant increases of regional cerebral blood flow were found in the contralateral sensorimotor cortex and bilateral inferior parietal cortex. A region that was activated at PET 2 only was found in the ipsilateral premotor area. Recovery from hemiplegia is accompanied by changes of brain activation in sensory and motor systems. These alterations of cerebral activity may be critical for the restoration of motor function.