We are investigating the potential of in vivo proton magnetic resonance spectroscopy for noninvasive characterization of the chemical pathology of plaques in magnetic resonance brain images from patients with multiple sclerosis. Spectra localized to chronic, irreversible plaques showed a decrease in the ratio of N-acetyl/creatine resonance intensities relative to normal-appearing white matter. Spectra localized to active plaques showed different metabolite changes as compared with spectra from identical, plaque-free volumes in the contralateral hemispheres. Some active plaques showed either no abnormalities or only an increase in tissue lactate. Spectra from others showed an increased ratio of choline/creatine resonance intensities, with or without a decreased N-acetyl/creatine resonance intensity ratio. In one case, serial observations showed an evolution of changes in spectra from a single plaque from an increased choline/creatine ratio to a decreased N-acetyl/creatine ratio. These observations suggest that proton magnetic resonance spectroscopy may be able to distinguish acute or active from chronic plaques and to characterize the pathologic evolution of active plaques by measurement of local tissue metabolite levels.