Pain-related somatosensory evoked potentials (SEPs) following CO2 laser stimulation were analyzed in normal volunteers. Low power and long wavelength CO2 laser stimuli to the hand induced a sharp pain which was associated with a large positive component, P320, recorded over the scalp. Amplitude decreased and latency increased with reduction in stimulus intensity and subjective pain feeling. P320 was maximal at the vertex but was distributed widely over the scalp. There were no topographic differences between left- and right-hand stimulation, or between hand and chest stimulation. Lidocaine injection to produce anesthetic nerve block resulted in loss of P320, but the potential was relatively preserved during ischemic nerve block. No potential corresponding to P320 could be recorded following electrical or mechanical tactile stimulation. We consider P320 to be generated by impulses arising from pain stimuli and ascending through A delta fibers. We propose the thalamus as a generator source from considering its scalp topography, but pain-specific cognition or perception may also be involved in generating this potential.