We studied responses of the parieto-frontal opercular cortex to CO2-laser stimulation of A delta fiber endings, as recorded by intra-cortical electrodes during stereotactic-EEG (SEEG) presurgical assessment of patients with drug-resistant temporal lobe epilepsy. After CO2-laser stimulation of the skin at the dorsum of the hand, we consistently recorded in the upper bank of the sylvian fissure contralateral to stimulation, a negative response at a latency of 135 +/- 18 ms (N140), followed by a positivity peaking around 171 +/- 22 ms (P170). The stereotactic coordinates in the Talairach's atlas of the electrode contacts recording these early responses covered the pre- and post-rolandic part of the upper bank of the sylvian fissure (-27 < y < +12 mm; 31 < x < 57 mm; 4 < z < 23 mm), corresponding to the accepted localization of the SII area in man, possibly including the upper part of the insular cortex. The spatial distribution of these early contralateral responses in the SII-insular cortex fits wit that of the modeled sources of scalp CO2-laser evoked potentials (LEPs) and with PET data from pain activation studies. Moreover, this study showed the likely existence of dipolar sources radial to the scalp surface in SII, which are overlooked in magnetic recordings. Early responses also occurred in the SII area ipsilateral to stimulation peaking 15 ms later than in contralateral SII, suggesting a callosal transmission of nociceptive inputs between the two SII areas. Other pain responsive areas such as the anterior cingulate gyrus, the amygdala and the orbitofrontal cortex did not show early LEPs in the 200 ms post-stimulus. These findings suggest that activation of SII area contralateral to stimulation, possibly through direct thalamocortical projections, represents the first step in the cortical processing of peripheral A delta fiber pain inputs.