The aim of this investigation was to compare two current non-invasive modalities, single photon emission tomography (SPECT) using 123-iodine-alpha-methyl tyrosine (123I-IMT) and single-voxel proton magnetic resonance spectroscopy (1H-MRS) at 3.0 T, with regard to their ability to differentiate between residual/ recurrent tumors and treatment-related changes in patients pretreated for glioma. The patient population comprised 25 patients in whom recurrent glioma was suspected based on MR imaging. SPECT imaging started 10 min after iv. injection of 300-370 MBq 123I-IMT and was performed using a triple-head system. The IMT uptake was calculated semiquantitatively using regions-of-interest. 1H-MRS was performed at 3.0 T using the single-volume point-resolved spectroscopy (PRESS) technique. Guided by MR imaging volumes-of-interest for spectroscopy were placed into the suspected lesions. Signal intensities of choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and N-acetylaspartate (NAA) were obtained. When using the cut-off of 1.62 for 123I-IMT uptake, the sensitivity, specificity, and accuracy of the 123I-IMT SPECT were 95, 100 and 96%, respectively. For 1H-MRS, the sensitivity, specificity and accuracy were 89, 83 and 88%, respectively, based both on the metabolic ratios of Cho/Cr and Cho/NAA as tumor criterion with cut-off values of 1.11 and 1.17, respectively. In conclusion, 123I-IMT SPECT yielded more favorable results compared to 1H-MRS at distinguishing recurrent and/or residual glioma from post-therapeutic changes and may be particularly valuable when the evaluation of tumor extent is necessary.