The clinical usefulness of L-methyl-11C-methionine positron emission tomography (11C-MET PET) and thallium-201 single photon emission computed tomography (201T1 SPECT) for distinguishing glioma recurrence from radiation-induced changes was evaluated. Ten patients with lesions highly suggestive of recurrent glioma on magnetic resonance imaging underwent 11C-MET PET and 201T1 SPECT studies. Two patients were examined twice, so a total of 12 studies were performed. The clinical diagnoses were five recurrent gliomas and seven radiation necrosis. The five recurrent gliomas appeared as increased uptakes on both 11C-MET PET and 201T1 SPECT scans. Four of the seven radiation necrosis lesions also appeared as increased uptakes on the 201T1 SPECT scans. In contrast, only one radiation necrosis appeared as increased uptake on the 11C-MET PET scans. There was no significant difference in 201T1 SPECT indices between radiation necrosis and tumor recurrence, but the ratio of the differential absorption ratio of tumor tissue to that of the homologous contralateral gray matter in PET of recurrent glioma was significantly higher than that of radiation necrosis. 11C-MET PET is superior to 201T1 SPECT for the differentiation of tumor recurrence from radiation necrosis and delineation of the extent of the tumor.