We used proton magnetic resonance (MR) spectroscopic imaging to determine the serial changes in MR signals from choline, creatine, lactate, and N-acetylaspartate in and around a large demyelinating lesion followed over a period of 8 months. Elevated lactate and choline signals were observed at the first examination 3 days after the onset of symptoms. Reduced N-acetylaspartate signals were observed a few days afterward. The abnormal metabolite signals varied in different regions of the lesion and extended beyond the borders of abnormal signal intensity seen on conventional MR imaging (MRI). On the last examination at 8 months when the lesion appeared much smaller on MRI, choline signals from the center of the lesion were still high, but were falling. Choline signals outside the lesion on MRI had returned to normal as had lactate signals everywhere. Importantly, there was no recovery of N-acetylaspartate signals in or adjacent to the lesion on MRI. This serial study demonstrates the potential of MR spectroscopic imaging for characterizing the chemical pathological evolution of demyelinating lesions in ways that conventional MRI cannot. We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N-acetylaspartate can provide an index of irreversible damage in the nervous system.