Focal cortical disturbances are frequent sequelae in West syndrome (WS) even though it is a generalized epileptic syndrome. Functional neuroimaging was used to determine whether focal perfusion abnormalities exist at WS onset and change during evolution. We studied regional cerebral blood flow (rCBF) at different stages of WS. Mean CBF (mCBF) and rCBF were measured using SPECT (single photon emission computed tomography) and 133Xe in 13 WS patients: at onset (20 cases), just after steroids (17 cases), and after a mean follow-up of 2 years (26 cases). At WS onset, interictal mCBF was increased as the result of foci of hyper- and hypoperfusion, which were, respectively, mainly located in the frontal and posterior cortex. Just after steroid therapy, mCBF decreased without any focal predominance. During follow-up, hypoperfused foci remained unchanged whereas the frontal hyperperfused foci decreased after spasm control. Our results show that focal abnormalities are present at WS onset. Focal hypoactivity could reflect a cortical lesion responsible for WS and focal hyperactivity could play a role in the persistence of generalized epilepsy.