Background The local cortical activation-inhibition sequence underlying electrically evoked cortico-cortical potentials (CCEPs) is little known in humans. Our aim was to study these physiological mechanisms in drug-resistant epileptic patients implanted with subdural electrodes. Materials and methods To reveal the effect of cortical electrical stimulation (CES) we used intracortical laminar multielectrodes. We studied the effect of CES, applying single (10 mA, 0.5 Hz) and paired (ISI: 7–1000 ms) pulses on subdural electrodes. We analyzed the cortical depth distribution of local field potentials, current source density (CSD), changes in spectral power, and in multiple and single unit activity (MUA and SUA) in the time window of CCEPs. Results The laminar profile of the CCEPs showed a surface current source and middle layer sink (P1) followed by surface sink and a layer IV source (N1) associated with an increase in MUA and SUA, a surface source and a layer IV sink (P2) subsequently a cortical wide source in the middle layers (N2) accompanied by MUA and SUA decrease and a middle layer sink and increase in MUA and SUA for P3. In paired pulse setting, the amplitude differences of N1-P2 were correlated with ISI. We found similar N1-P2 curve in 8 out of 10 patients characterized by an excitation at ISI 7–10 ms, inhibition at 20–50 ms and a long interval excitation at 200–500 Conclusions We identified both excitatory (P1, N1, P3) and inhibitory (P2, N2) CCEP components. In our paired pulse stimulation setting we demonstrated these inhibitory and excitatory effects on the second CCEP response.