Nocigenic inhibition is the inhibition of neural, behavioral, or reflex responses to a nociceptive test stimulus produced by another, conditioning, nociceptive stimulus. The present study examines whether a natural noxious visceral stimulus, colorectal distension, used as a conditioning stimulus would inhibit neuronal or reflex responses to noxious cutaneous stimuli. Segmental effects of colorectal distension have been previously characterized; hence conditioning effects of colorectal distension on stimuli applied at sites distant (heterosegmental effects) and adjacent (perisegmental effects) to those areas of the spinal cord that receive the greatest afferent input from the colon were examined. The conditioning effects of colorectal distension were compared with those of noxious pinch. Heterosegmental effects of colorectal distension were studied in 129 neurons located in the area of the trigeminal nucleus caudalis and cervical spinal dorsal horn. Steady-state activity (spontaneous activity or activity evoked by sustained pressure) of 106 of 129 trigeminal-cervical dorsal horn neurons was inhibited by both noxious colorectal distension (100 mmHg, 20 s) and noxious pinch of the tail; all neurons inhibited by colorectal distension were also inhibited by noxious pinch. Inhibition was graded with the intensity of the distending stimulus. The class 2-class 3 classification system (neurons excited by nonnoxious and noxious or only by noxious cutaneous stimuli, respectively) was roughly predictive of susceptibility to nocigenic inhibition, because 74 of 75 class 2 neurons tested were inhibited by noxious colorectal distension or noxious pinch and only 32 of 54 class 3 neurons were similarly inhibited. Five neurons were excited by colorectal distension, all of which were class 3 neurons. Perisegmental effects of colorectal distension were observed in 100 L3-L5 spinal dorsal horn neurons. The spontaneous activities and responses during noxious test heating of the glabrous skin of the hindpaw of these neurons were affected in the same way by noxious (conditioning) colorectal distension. All neurons inhibited by colorectal distension (51 class 2 and 8 class 3 neurons) were also inhibited by noxious pinch of the nose or forepaw. The magnitude of the nocigenic inhibition of responses during heating of the hindpaw was graded with the intensity and duration of the noxious conditioning colorectal distension, was a function of the number of preceding distensions given to the rat, and outlasted the distending stimulus. Conditioning colorectal distension also produced a parallel shift to the right in stimulus-response functions relating responses of neurons to the intensity of the noxious test stimulus (42-50°C). In 41 other neurons (23 class 2 and 18 class 3 neurons), colorectal distension produced excitation or had no effect. Of these, 20 class 2 and 12 class 3 neurons were inhibited, whereas the remaining 3 class 2 and 6 class 3 neurons were unaffected or excited by noxious pinch of the nose or forepaw. Both noxious conditioning colorectal distension (100 mmHg) and noxious pinch of the nose inhibited the reflex withdrawal of the tail to noxious heat. Similar to the inhibition of lumbar dorsal horn neuronal activity, inhibition of the nociceptive tail flick reflex produced by noxious conditioning colorectal distension was a function of the intensity and duration of the distending stimulus, the number of preceding colorectal distensions given, and outlasted the distending stimulus. Nocigenic inhibition of lumbar spinal dorsal horn neurons and the tail flick reflex produced by noxious colorectal distension was demonstrated to have both spinal and supraspinal components. Reversible spinalization (cervical cold block) produced a significant reduction but failed to abolish nocigenic inhibition of either the tail flick reflex in five rats or the responses of 10 L3-L5 spinal dorsal horn neurons during heating of the skin of the hindpaw. These data, coupled with previous reports, demonstrate that nocigenic inhibition of spinal visceral and cutaneous nociception is indistinguishable. In the special case of nocigenic inhibition produced by noxious colorectal distension, we speculate that this inhibition is mediated by spinal neurons with sustained after-discharges and large receptive fields responding only to noxious inputs; these neurons are likely a subset of neurons previously described as short latency-sustained neurons.