Summary: Purpose: To study in humans the hemodynamic and metabolic consequences of both photic stimulationtriggered and spontaneous generalized epileptiform discharges.Methods: Simultaneous EEG, functional magnetic resonance imaging (fMRI) and MR spectroscopy were performed in a 1.5-T scanner in 16 patients with generalized epilepsy, including nine with photosensitive epilepsy, and 12 normal subjects.Results: With a flash stimulation duration of 2 s, prominent visual cortex activation was seen in all normals and patients. There were no fMRI-registered hemodynamic abnormalities found in relation to the brief photoparoxysmal spike-wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike-wave response to the photic stimulation, the photosensitive patients showed four unique findings compared with normals: (a) slightly, but significantly, increased lactate levels in the occipital cortex in the resting state, (b) an increased area of visual cortical activation with photic stimulation, (c) simultaneous with the occipital cortex stimulus-induced increased fMRI signal there were noncontiguous areas of signal attenuation most prominent in perirolandic regions, and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyms.Conclusions: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients. Key Words: Functional MRI-MR spectroscopyGeneralized epilepsy-Photosensitive-EEG.Most studies of the pathophysiology of the generalized epilepsies in humans have used positron emission tomography (PET) and fluorodeoxyglucose (FDG). In the interictal periods, these investigations showed a normal cerebral metabolic rate for glucose (CMRGlc) (1-3), and during ictal episodes of various types showed both increased and decreased CMRGlc and cerebral blood flow (CBF) (1-7). Thus these data suggest that further investigations in the human generalized epilepsies might advance the understanding of their pathophysiologies.Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) are noninvasive and require no isotopes or contrast agents. fMRI has a spatial resolution of a few millimeters or less and a