Inflammatory reactions are involved in the pathogenesis of cerebral ischemia. Cytokines exacerbate brain ischemic injury by several mechanisms and they activate the synthesis of acute-phase reactants. We evaluated the association between cytokine-induced inflammation and functional outcome in 41 patients with acute ischemic stroke. Blood samples for interleukin-1 receptor antagonist (IL-1ra), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and polymorphonuclear leukocyte (PMNL) count were taken within 48 h from stroke onset. Functional outcome was assessed at six months with the Modified Rankin Scale. Patients with a Rankin score > or = 3 were classified as dependent outcome. The effect of inflammatory variables on outcome was analyzed by logistic regression. Mathew score <75 on admission, atrial fibrillation, non-lacunar infarct size, ESR>13 mm/h in men or >20 mm/h in women, PMNL count >8 x 10(9)/l, CRP>0.8 mg/dl and IL-1ra>500 pg/ml were associated with dependent outcome. On multiple logistic regression, severe stroke on admission, non-lacunar infarct size and ESR remain in the predictive model of outcome with a sensitivity and specificity of 76 and 80%, respectively. This study suggests that in addition to clinical evaluation and neuroimaging, measurement of ESR may be useful for the early detection of stroke patients with poor long-term functional outcome.