Despite encounter of novel brain antigens by the systemic immune system following stroke, autoimmune responses to these antigens do not seem to occur. In rats, a systemic inflammatory response at the time of stroke, however, provokes changes that increase the likelihood of developing detrimental autoimmunity. These findings may help to explain why infections in the post-stroke period are associated with worse outcome. In addition, data suggest that the immune response can be manipulated in an antigen specific fashion to improve stroke outcome. Together these data argue that the nature of the post-ischemic immune response influences neurological recovery from stroke. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.