Periodic lateralized epileptiform discharges (PLEDs) are a well defined electroencephalographic entity but whether PLEDs represent an ictal condition or not remains debated. Much work has been done using electroencephalography (EEG) but new approaches using cerebral perfusion imaging may give more information about this question. We aimed to evaluate if PLEDs were associated with high regional cerebral blood flow (rCBF). We studied 18 patients with PLEDs and different pathologies, and performed brain single-photon-emission computed tomography (SPECT) during and, for three cases, after the disappearance of PLEDs. Qualitative variations and locations of rCBF were compared with PLEDs. Association with seizures and type of seizures were also assessed. SPECT showed high rCBF in 18/18 patients (100%). The location of PLEDs and high rCBF matched in 17/18 cases (94%). In the three cases where SPECT was performed after PLEDs disappeared, the high rCBF had cleared (100%). Eighteen cases (100%) presented seizures before recording of PLEDs, mainly motor (partial motor or generalized tonic-clonic). Where there was a decreased rCBF (related to a lesion) there was little relationship to PLEDs and all patients with decreased rCBF had an adjacent increased rCBF. These results confirm preliminary case reports. Hyperperfusion adds further to the argument that PLEDs may be related to a form of partial status epilepticus.