Objective: The splenic response to injury furthers cellular degeneration as its removal is protective in ischemic injuries to several organ systems including the brain. Previously, we have shown that the proinflammatory cytokine interferon gamma (IFNg), which activates microglia/macrophages, is elevated in the spleen and the brain following permanent middle cerebral artery occlusion (MCAO). IFNg induces the production of interferon-inducible protein 10 (IP-10) which further propagates the inflammatory response. Therefore, we investigated the expression of IP-10 in the brain and spleen following ischemic stroke. Hypothesis: IFNg production in the brain and the spleen results in elevated levels of IP-10 in the same tissues post-MCAO. Methods: A time course was conducted to investigate splenic and brain protein levels of IP-10 in rats over time following MCAO and sham-MCAO (n≥3). In a second experiment, rats were administered an IFNg neutralizing antibody following MCAO with a survival time of 96 h: vehicle control (n=4), goat IgG 5μg (n=7), and IFNg antibody 5μg (n=7). Spleens and brains were collected for all groups. Results: IP-10 levels were significantly elevated in the brain at 72 and 96 h post-MCAO (p<0.01) compared to naïve brains. In the spleen IP-10 levels become significantly elevated at 24 h and remain elevated out to 96 h post-MCAO (p<0.0007) compared to naïve spleens. Administration of a neutralizing antibody directed against IFNg significantly decreased IP-10 levels in the brain (p<0.009) but did not affect IP-10 levels in the spleen. Conclusion: These results demonstrate that increased production of IFNg results in elevated levels of IP-10 in both the spleen and the brain following stroke. However, administration of a neutralizing antibody against IFNg decreased the amount of IP-10 in the brain. Levels of IFNg and IP-10 in the brain increase at the same time following stroke. Based on these data, IFNg propagates a proinflammatory T helper cell response to stroke through IP-10. Inhibition of this signaling could reduce neuroinflammation thereby improving stroke outcome.