Introduction Only few studies have explored the pathophysiology of PSE; some Authors have suggested a defective visual inhibition as a contributing factor to photoparoxysmal response, pointing to an overactive visuomotor connectivity thus inducing abnormal motor responses. In order to investigate functional changes underlying photosensitivity, we studied the response of the visual cortex to low-frequency, inhibitory repetitive transcranial magnetic stimulation (rTMS) in drug-free patients with photosensitive seizures and healthy volunteers. Methods Visual evoked potentials (VEPs) triggered by grating stimuli of different luminance contrasts (K20%, K50% and K90%) were recorded in both hemispheres before and after transient functional inactivation of the occipital cortex of one side via low-frequency rTMS (0.5 Hz, at 120 % of resting motor threshold, for 20’). VEPs were recorded before (T0), immediately after (T1) and 45’ following the completion of rTMS (T2). The display was either centered on the vertical meridian (central stimulation) or positioned in the right hemifield (with its inner edge at a distance of 1 degree from the fixation point). Results Baseline amplitudes of the VEP components (N1 and P1) were enhanced in photosensitive patients. At T1, rTMS produced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a concurrent facilitation of responses in the contralateral hemisphere. Compared with PSE subjects, VEP amplitudes remained persistently dampened in the stimulated hemisphere of controls (Holm–Sidak post hoc method, p Conclusion The rapid recovery of excitability and the persistent transcallosal disinhibition following perturbation of cortical activity may play a role in the pathophysiology of photosensitive epilepsy. Beyond the stereotyped dichotomy between generalized and focal epilepsies, our data seem to indicate PSE as a “system disease”.