Based on intracellular recordings in vivo, we investigated the responsiveness of cat neocortical neurons to callosal volleys during different phases of spontaneously occurring or electrically induced electrographic seizures, compared with control periods of slow sleep-like oscillations. Overt seizures, with spiking, triggered by pulse-trains to the callosal pathway, started with a latency of approximately 20 s after cessation of stimulation, thus contrasting with paroxysmal activity elicited by ipsilateral cortical or thalamic stimulation that is initiated immediately after electrical stimulation. During the rather long preparatory period to callosally triggered seizures, cortical neurons displayed subthreshold depolarizing runs at 4-7 Hz, associated with increased amplitudes of excitatory postsynaptic potentials. The sequential analysis of neuronal responsiveness during different components of spike-wave complexes revealed progressively increased amplitudes of callosally evoked postsynaptic excitatory responses in regular-spiking and fast-rhythmic-bursting neurons, over a period of approximately 20 ms prior to the generation of paroxysmal depolarizing shifts. These data support the concept that seizures consisting of spike-wave complexes originate within the neocortex through a progressive synaptic buildup and that their synchronization is achieved, at least partially, by cortical commissural synaptic linkages. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.