Multicontact microelectrodes were chronically implanted in epilepsy patients undergoing subdural grid implantation for seizure localization. Current source density and multiple unit activity of interictal spikes (IISs) were sampled every approximately 150 microm in a line traversing all layers of a cortical column. Our data suggest that interictal epileptiform events in humans are initiated by large postsynaptic depolarizations, consistent with the hypothesis that human IISs correspond to animal paroxysmal depolarization shifts. Furthermore, the cortical layer where the initial depolarization occurs may differ according to whether the IIS is locally generated or propagated from a distant location, and among the propagated IISs, whether the IIS is in the direct path of propagation or on the periphery of that path.