The pathophysiological basis of the epileptic encephalopathy West's syndrome remains unknown. We have done serial positron emission tomography (PET) with fluorine-18-labelled 2-deoxy-3-fluoro-D-glucose (FDG) in twelve patients with newly diagnosed West's syndrome. Throughout follow-up, PET revealed diffuse or focal cortical hypometabolism in eleven patients, whereas magnetic resonance imaging (MRI) showed morphological abnormalities in only five. At disease onset, PET showed cortical hypometabolism in eight patients (diffuse in three, focal in five). The second PET showed normal metabolism in six of these patients but focal abnormalities in three of the four with normal results on first PET. In all seven patients with normal findings on the second PET, tonic spasms ceased after initial treatment and no epileptic seizure occurred thereafter. In the five patients with cortical hypometabolism on the second PET, tonic spasms persisted or recurred, or partial seizures appeared. However, in two patients PET abnormalities disappeared in accordance with the later resolution of epileptic seizures. All patients with normal MRI and second PET results had normal psychomotor development. Diffuse or focal cortical hypometabolism that cannot be detected by MRI or computed tomography is common in patients with West's syndrome. However, this anomaly is not permanent and changes with clinical symptoms. These functional abnormalities in the cerebral cortex may be associated with the development of West's syndrome.