1. Twenty-six nociceptive neurons in the primary somatosensory cortex (SI) of anesthetized monkeys were responsive to noxious thermal stimulation applied to the face. Thermode temperature increased from a base line of 38 degrees C to temperatures ranging from 44 to 49 degrees C (T1). After a period of 5 s, the temperature increased an additional 1 degree C (T2). The neuronal responses to noxious thermal stimuli were compared when the interstimulus interval (ISI) was 30 or 180 s. 2. A linear regression analysis was applied to the stimulus-response functions of neuronal responses to T1 stimuli obtained at ISIs of 180 s. Based on the slopes and linear regression coefficients of these stimulus-response functions, two populations of nociceptive neurons were identified. The neuronal responses of one population of nociceptive SI neurons (WDR1) to T1 stimuli were characterized by steep slopes and high regression coefficients, whereas the other population (WDR2) had flatter slopes and lower regression coefficients. WDR1 neurons responded with monotonic increases in neuronal activity as the stimulus intensity increased. However, the peak frequency of WDR2 neurons often reached a plateau below 47 degrees C. Both WDR1 and WDR2 neurons had receptive fields that encompassed one or two divisions of the trigeminal nerve. 3. The T1 neuronal responses of WDR1 neurons were significantly suppressed when thermal stimuli were delivered with ISIs of 30 s. The T1 neuronal responses of WDR2 and the T2 responses of both WDR1 and WDR2 neurons were not significantly different when ISIs of 30 and 180 s were used. The T1 thresholds of WDR1 and WDR2 neurons were significantly higher when stimuli were delivered with ISIs of 30 s compared with ISIs of 180 s. 4. Most nociceptive SI neurons were located in layers III and IV of area 1-2. In a number of instances, multiple nociceptive neurons were found in the same microelectrode penetration. 5. The humans' intensity of pain sensation paralleled the neuronal responses of nociceptive SI neurons. With the use of a similar paradigm as in the monkey experiments, increases in T1 and T2 temperatures resulted in monotonic increases in pain ratings and change in pain sensation, respectively. However, the intensity of pain sensation to T1 temperatures was suppressed by ISIs of 30 s. Neither ISI produced statistically significant changes in the intensity of pain sensation to T2 stimuli. 6. These data demonstrate that manipulations that alter the intensity of pain sensation also produce concomitant changes in the responsiveness of nociceptive SI neurons.(ABSTRACT TRUNCATED AT 400 WORDS)