Several studies have shown that the prognosis of oligodendrogliomas is dependent on their histological grade. In order to identify a non-invasive method for the primary diagnosis and follow-up of these tumours, we investigated the relationship between their in vivo metabolism, assessed by positron emission tomography (PET), and their histological grade assessed at the same time. Forty-seven patients with histologically confirmed oligodendrogliomas were investigated. Conventional neuroradiological assessment by computed tomography and magnetic resonance imaging (MRI) was performed in all the patients. All the histology slices were reviewed by the same pathologist after referral from various pathology laboratories. The PET investigation included a carbon-1 methionine (11C-MET) uptake study and, in the majority of cases, a fluorine-18 fluorodeoxyglucose (18F-FDG) uptake study, in order to investigate at the same time both amino acid metabolism and glycolysis. The sampled tumour region of interest (ROI) was defined from the T1-weighted 3D MR scan matched with the PET scan. Tracer concentration in each voxel of the tumour ROI was divided by the mean concentration in an ROI of the same size located in the healthy brain tissue. For each tumour and each tracer, we characterized the metabolic pattern on the basis of the mean and the maximum tumour to healthy tissue concentration ratio, and also the standard deviation and range of the ratios, which indicate the degree of metabolic heterogeneity of the tumour. The histological criteria for differentiating between high- and low-grade tumours were those of the WHO and, partially, of the Sainte-Anne-Daumas-Duport classification. Highly significant differences between high- and low-grade oligodendrogliomas (Mann-Whitney test: P<0.0001) were observed for all the assessed parameters of 11C-MET uptake. On the other hand, the pattern of 18F-FDG uptake showed only moderate differences between the two tumour groups.