Information about noxious events in the periphery is conveyed to the spinal cord in A- and C-fibre nociceptive afferents, which have largely distinct electrical and chemical properties and which convey different qualities of the pain signal. Descending control that originates in the different functional columns of the midbrain periaqueductal grey (PAG) has important roles in the modulation of spinal nociception in different behavioural and emotional states and, it is now believed, in animal models of chronic pain. However, few studies of descending control have considered differential modulation of A- versus C-nociceptor-evoked responses. Here, we report that descending inhibitory control from the rostrocaudal extent of the dorsolateral/lateral and ventrolateral columns of the PAG preferentially targets Class 2 deep dorsal horn neurons with C-fibre inputs. Pinch-evoked responses of these neurons were depressed significantly by -37+/-4.2% (P<0.0001). In contrast, the pinch-evoked responses of Class 2 neurons without C-fibre inputs (presumably A-fibre mediated) were enhanced significantly by +34+/-11.8% (P<0.01). Further experiments indicated these facilitatory effects were at least partly due to a reduction in C-fibre-mediated segmental inhibition. We suggest this differential control of spinal nociception would be appropriate in many of the varied situations in which the PAG is believed to become active, whether short term (e.g. fight or flight) or long term (e.g. chronic pain). Additionally, the pro-nociceptive effects observed in a subset of spinal neurons may be related to the descending facilitation that has been reported in animal models of chronic pain.