We studied the spectroscopic appearance of radiation-induced myelinolysis in cats to understand the characteristics of proton MR spectroscopy of demyelinating disorders. Eight cats received 5,000 rads to a 1.5 x 1.5 cm area of the right cerebral hemisphere. Eight to 9 months after irradiation, a gross area of abnormal postcontrast enhancement and/or high MR signal intensity was detected in the irradiated hemisphere of six of the eight cats. Proton spectra of a 1.0 cm3 voxel in the affected region demonstrated depressed N-acetyl aspartate/creatine-phosphocreatine and N-acetyl aspartate/choline-containing compound peak ratios compared with the contralateral non-irradiated brain in all cats. Elevated amino acid resonances in the 2.0-2.5 ppm range were not consistently seen in irradiated zones of the brain with pathologic findings of demyelination. In vivo proton MR spectroscopy may show differences between irradiated brain and nonirradiated brain even when histopathologic lesions are not apparent yet.