The role of the red nucleus (RN) in nociception was investigated in this study. Extracellular recordings from spontaneously active RN neurons were conducted in the rat while noxious pressure was delivered to the hindpaws or tail. Cells in the RN were predominantly inhibited by the stimuli. The units were most responsive when noxious pressure was applied to the contralateral hindpaw. Furthermore, more cells in the magnocellular division of the RN responded to the stimuli than cells in the parvocellular division. Delivery of a graded pressure stimulus to the contralateral hindpaw revealed 4 cell types in the RN: non-responsive cells; cells only responsive during the early, non-noxious portion of the stimulus; cells only responsive during the later, noxious portion of the stimulus; and cells that showed an initial response during the non-noxious part of the stimulus and a second, later response during the noxious portion of the stimulus. To further examine the putative role of the RN in nociception, oxotremorine, gamma-aminobutyric acid (GABA), serotonin, glutamate, and morphine were unilaterally microinjected into the RN and the responses of the animals in the tail flick test were assessed. Only morphine produced a significant antinociception in the animals following intrarubral microinjection. However, it is unclear whether this alteration was mediated through the RN because an antinociception of equal magnitude could be elicited from the reticular formation surrounding the RN and lesions of the RN did not alter the antinociception produced by systemic administration of morphine. Although other explanations cannot be ruled out, it appears that the RN may be involved in coordinating the motor response to pain rather than modulating sensory transmission.