Local microinjection of GABAA receptor agonists and antagonists was used to characterize the role of GABA-mediated inhibitory processes in the nociceptive modulatory functions of the rostral ventromedial medulla (RVM) in the lightly anesthetized rat. Microinjection of selective GABAA receptor antagonists bicuculline methiodide and SR95531 produced a significant increase in tail-flick (TF) latency. This antinociception was dose related, showed recovery and was attenuated by prior injection of the GABAA receptor agonist THIP at the same site. Microinjection of saline or the glycine receptor antagonist strychnine did not significantly affect TF latency. In contrast, administration of GABAA receptor agonists THIP and muscimol resulted in a significant decrease in TF latency. Microinjections at sites surrounding the RVM did not significantly affect TF latency. These results demonstrate that a GABA-mediated process within the RVM is crucial in permitting execution of the TF and, presumably, other spinal nociceptive reflexes.