The anterior cingulate cortex (ACC) is implicated in the processing and modulation of the emotional reaction to pain in both humans and animals. The ACC is divided into rostral (perigenual) and caudal (midcingulate) regions based on anatomy and function. Recent evidence suggests that activation of the caudal ACC (cACC) contributes to nociceptive processing, whereas activation of the rostral ACC (rACC) mediates antinociception. In the present study, we compared the antinociceptive action of NMDA and the NMDA receptor antagonist AP5 administered into the cACC and rACC. Pain behaviors organized at spinal (spinal motor reflexes = SMR), medullary (vocalizations during shock = VDS), and forebrain (vocalizations afterdischarges = VAD) levels of the neuraxis were elicited by tailshock. VADs are a validated rodent model of pain affect. The threshold current intensity to elicit each behavior was determined following bilateral microinjections of NMDA, AP5 or NMDA + AP5 into the rACC or cACC. Administration of NMDA into the rACC (0.5 μg/.25 μl) elevated VAD and VDS thresholds, but failed to increase SMR threshold. VAD threshold was elevated to a greater degree than VDS threshold. NMDA-induced increases in vocalization thresholds were blocked by prior administration of AP5 (4 μg in 0.25 μl/side) into the rACC. Administration of AP5 alone into the rACC did not alter any response threshold. Alternately, administration of AP5 alone into the cACC elevated VAD and VDS thresholds, but did not increase SMR threshold. VAD threshold was elevated to a greater degree than VDS threshold. AP5-induced increases in vocalization thresholds were blocked by administration of NMDA into the cACC. These findings indicate that there are regional differences within the ACC with regard to the processing and modulation of pain affect. NMDA receptor activation in the rACC suppresses pain affect; whereas, NMDA receptor activation within the cACC contributes to generation of pain affect.