Despite apparent relationships between ischemic stroke and the acute phase response (APR), considerable variation in the APR exists between individuals. We therefore performed post-hoc analysis of individual APR profiles in 31 patients with ischemic stroke in relation to volume of brain infarction. Patients with ischemic stroke had serial blood samples taken within 12 h, and up to 12 months of symptom onset, for analysis of plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Computed tomography (CT) brain infarct volume was measured at 5 to 7 days (median 23.9 cm(3)). An increase in plasma CRP after the admission sample was evident in 94% of patients by day 5 to 7 (median increase 558% of admission value). CRP response, assessed as area under the curve between admission and day 5 to 7, correlated strongly (r=0.62, p<0.001) with CT infarct volume. Those with greater infarct volumes had more evidence of infection, either prior to or during the first week after stroke. The pattern of response was similar for IL-6, although only 77% showed an increase in plasma IL-6 after the admission sample (median increase 148% of admission value). These data suggest that, although infection and other factors may contribute to systemic inflammation, the extent of acute brain injury after ischemic stroke is a major factor influencing the magnitude and variability of the APR.