Both interictal and ictal Tc-99m-HMPAO brain SPECT were performed in 22 patients with medically intractable epilepsy. Localization of epileptic foci in our patients was made by combined results of EEG and other tests, including Wada test, magnetic resonance imaging, and neuropsy- chometric test. Among them, ictal Tc-99m-HMPAO SPECT, localized epilptic foci in 20 of 22 patients and provided evidence of epileptic focus in 12 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci during the ictal study with decreased rCP in interictal study. Ictal Tc-99m-HMPAO SPECT Was particularly useful for investigating epileptic foci, and when correlated with simultaneously recorded ictal EEG, provided further insight for localizing epileptic foci. Conclusively, Tc-99m-HMPAO SPECT is a useful, noninvasive method of localizing epileptic activity which may be particularly important for presurgical investigations, especially in those patients without large morphological lesions.