To identify the focus of paroxysmal neuronal activity causing epilepsy in tuberous sclerosis (TS), the regional cerebral blood flow (r-CBF) in 19 patients with TS was assessed using single-photon emission computed tomography (SPECT) with I-123 iodoamphetamine (IMP), in correlation with serial interictal EEGs and organic changes observed on magnetic resonance imaging (MRI). There was a general irregularity of cortical IMP uptake and retention in TS, and two-thirds of the cerebral regions exhibiting high intensity in T2-weighted MRI images (cortical tubers) showed a decrease in r-CBF. In addition to in tubers, decreased r-CBF was observed in regions in which MRI was considered to indicate destruction of the normal cortex, atrophy or vascular abnormalities, although these areas did not consistently show epileptic changes in serial EEGs. Among the cortical regions which consistently showed epileptic foci in serial EEGs, none showed abnormal r-CBF without lesions on MRI. We conclude that IMP-SPECT is useful for visualizing the epileptogenic laterality in cases with bilateral MRI lesions and EEG epileptic changes, and to differentiate epileptogenic foci from electrophysiological propagated areas. However, regarding the severity of epilepsy, the MRI findings showed a better correlation than the IMP-SPECT findings did.