Our previous studies suggested that the cytokine tumor necrosis factor-alpha (TNF) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF is capable of affecting gastric function via the DVC circuitry has been impeded by the lack of an antagonist for TNF. The present studies used localized CNS applications of the TNF-adsorbant construct (TNFR:Fc) to attempt to neutralize the suppressive effects of endogenously produced TNF. Gastric motility of thiobutabarbital-anesthetized rats was monitored following systemic administration of lipopolysaccharide (LPS) to induce TNF production. Continuous perfusion of the floor of the fourth ventricle with TNFR:Fc reversed the potent gastroinhibition induced by LPS, i.e., central TRH-induced increases in motility were not inhibited. This disinhibition of gastric stasis was not seen following intravenous administration of similar doses of TNFR:Fc nor following ventricular application of the Fc fragment of human immunoglobulin. These results validate our previous studies that suggested that circulating TNF may act directly within the DVC to affect gastric function in a variety of pathophysiological states.