Fractalkine (FKN), also known as neurotactin, is a CX(3)C chemokine that exists in both secreted and neuronal membrane-bound forms and is upregulated during brain inflammation. There is accumulating evidence that FKN induces chemotaxis by binding to its receptor CX(3)CR1 on leukocytes and microglia. We generated FKN-deficient mice to study the role of FKN in postischemic brain injury. After transient focal cerebral ischemia, FKN-deficient mice had a 28% reduction in infarction size and lower mortality rate, when compared to wild-type littermates. The findings of this study indicate a possible role for FKN in augmenting postischemic injury and mortality after transient focal cerebral ischemia.