Single photon emission computed tomography (SPECT) has frequently been used to investigate cerebral brain perfusion (CBP) occurring ictally and inter-ictally in epileptic patients. Several studies have addressed the multimodal analysis of the modifications occurring in cerebral areas involved in seizure activity, by correlating SPECT with electroencephalografic (EEG) recordings during ictal and inter-ictal epileptiform lateralized discharges (IELDs). Although these studies have yielded interesting results, variations in regional CBP (rCBP) observed during ictal events are difficult to interpret since the areas of altered rCBP might reflect not only events restricted to the epileptogenic focus, but also large fluctuations determined by seizure spread. Inter-ictal rCBP correlates with the area generating the local EEG epileptogenic activity in a limited percentage of studies. Hyperventilation (HPV) represents a well established EEG activation procedure aimed at enhancing epileptiform discharges. Since HPV-enhanced IELDs may help analyze the CBP pathophysiology in inter-ictal epilepsy, in the present study we investigate this specific aspect co-registering EEG with SPECT in subjects affected by partial epilepsy responding to HPV with IELD enhancement without seizure precipitation. This study suggests a correlation between localized increase in rCBP and HPV-induced IELDs and provides a tool to discuss uncommon aspects of the physiology of rCBP during the inter-ictal state in the epileptogenic areas.