The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.