: Psychophysical experiments were carried out on 6 human subjects to determine how first and second pain are influenced by peripheral receptor mechanisms and by central nervous system inhibitory and facilitatory mechanisms. For these experiments, brief natural painful stimuli delivered to the hand were a train of 4-8 constant waveform heat pulses generated by a contact thermode (peak temp.= 51.5 [degrees] C). The magnitude of first and second pain sensations was estimated using cross-modality matching procedures and reaction times were determined. The latter confirmed the relationship between first and second pain and impulse conduction in A [delta] and C noxious heat afferents, respectively. The intensity of first pain decreased with each successive heat pulse when the interpulse interval was 80 sec or less. This decrease was most likely the result of heat induced suppression of A [delta] heat nociceptors since it did not occur if the probe location changed between successive heat pulses. In contrast, second pain increased in intensity with each successive heat pulse if the interval was 3 sec or less. This summation was most likely due to central nervous system summation mechanisms since it also occurred after blockage of first pain by ulnar nerve compression and when the location of the thermode changed between heat pulses. These observations and their interpretations are supported by our recording of responses of single A [delta] heat nociceptive afferents, C polymodal nociceptive afferents, and" warm" afferents of rhesus monkeys to similar trains of noxious heat pulses. Their responses to these heat pulses show a progressive suppression. Furthermore, previous studies have shown that wide dynamic range dorsal horn neurons show summated responses to repeated volleys in C fibers (Symbol). These spinal cord summation mechanisms could account for the summation of second pain.