The striatum is thought to play an important role in the spreading of epilepsy from cortical areas to deeper brain structures, but this issue has not been addressed with intracellular techniques. Paired recordings were used to assess the impact of cortical epileptiform activity on striatal neurons in brain slices. Bath-application of 4-amynopyridine (100 µM) and bicuculline (20 µM) induced synchronised bursts in all pairs of cortical neurons (up to 5 mm apart) in coronal, sagittal and oblique slices (which preserve connections from the medial agranular cortex to the striatum). Under these conditions, striatal medium spiny neurons (MSs) displayed a strong increased spontaneous glutamatergic activity. This activity was not correlated to the cortical bursts and was asynchronous in pairs of MSs. Sporadic, large-amplitude synchronous depolarisations also occurred in MSs. These events were simultaneously detected in glial cells, suggesting that they were accompanied by considerable increases in extracellular potassium. In oblique slices, cortically-driven bursts were also observed in MSs. These events were synchronised to cortical epileptiform bursts, depended on non-NMDA glutamate receptors, and persisted in the cortex, but not in the striatum, after disconnection of the two structures. During these bursts, MS membrane potential shifted to a depolarised value (59±4 mV) on which an irregular waveform, occasionally eliciting spikes, was superimposed. Thus, synchronous activation of a limited set of corticostriatal afferents can powerfully control MSs. Cholinergic interneurons located <120 µm from simultaneously recorded MSs, did not display cortically-driven bursts, suggesting that these cells are much less easily engaged by cortical epileptiform activity.