This study was performed to investigate the role of leukocyte accumulation in human cerebral infarction and its association with neurological functional outcome. A total of 42 patients diagnosed as acute ischemic stroke (22 embolism, 17 thrombosis, 3 TIA) were examined. Leukocyte accumulation was studied using indium-111-labeled leukocyte brain single-photon emission computed tomography (SPECT). Volume of brain infarction was evaluated by CT and/or MRI. The data were compared with the cerebral blood flow (CBF) imaging. Immediately after CBF study by SPECT using either technetium-99m hexamethylpropyleneamine oxine (Tc-99m-HMPAO) or technetium-99m ethyl-cysteinate dimer (ECD), In-111-labeled autologous leukocytes were injected intravenously. Brain scan for leukocytes was performed after 48 hours. The European Stroke Scale was used for neurological assessment. Thirteen patients with cerebral embolism and three patients with cerebral thrombosis showed intensive accumulation of leukocytes in the region of low flow. Leukocyte's accumulation was not seen in patients with TIA. The accumulation of leukocytes was more noticeable in the central zone of the ischemia. Patients who showed negative leukocyte accumulation revealed clinically mild functional outcome and the size of infarction on CT and/or MRI was small. The regional accumulation of leukocytes was seen in all the patients with hemorrhagic infarction, but the degree of hemorrhage on CT did not have significant influence on the amount of leukocyte accumulation. Abnormal accumulation of leukocytes was associated with reduced CBF during the acute embolic stroke. The present clinical study revealed that leukocyte accumulation correlated with the poor neurological functional outcome in patients with acute embolic stroke. The present study confirms that leukocytes contribute to the ischemic tissue damage of the brain and demonstrates a clinical evidence that the regional accumulation of leukocytes has a deleterious effect on the brain following ischemia.