Differential diagnosis between radiation necrosis and tumor recurrence is important in the clinical management of glioma. Multi-modality imaging including proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) with L-[methyl-(11)C]methionine (MET) was evaluated. Eighteen patients underwent sequential (1)H-MRS and MET-PET. The expressions of metabolites including choline-containing compounds (Cho), creatine phosphate (Cre), and lactate (Lac) were calculated as the ratios of Cho to Cre (Cho/Cre) and Lac to Cho (Lac/Cho). The uptake of MET was determined as the ratio of the lesion to the contralateral reference region (L/R). The final diagnoses were determined by histological examination and/or follow-up MR imaging and clinical course. The Lac/Cho ratio was 0.63 +/- 0.25 (mean +/- standard deviation) in recurrence (7 cases) and 2.35 +/- 1.81 in necrosis (11 cases). The Lac/Cho ratio was significantly different between the two groups (p < 0.01). Consecutive investigation of (1)H-MRS revealed temporary elevation of Cho in 4 of 9 cases of necrosis, which could be identified as false positive findings for recurrence. Including those cases, MET-PET demonstrated significant difference in the L/R ratio between the two groups (2.18 +/- 0.42 vs. 1.49 +/- 0.35, p < 0.01). According to a 2 x 2 factorial table analysis, the borderline values of Lac/Cho and L/R to differentiate recurrence from necrosis were 1.05 and 2.00, respectively. (1)H-MRS is reliable and accessible for the differentiation of recurrence and necrosis, although the temporary elevation of Cho in the course of necrosis should be recognized. Additional MET-PET imaging can establish the diagnosis.