Magnetization transfer imaging (MTI) was initially performed in normal guinea pigs and human volunteers. A magnetization transfer ratio (MTR) was calculated in the normal white matter and was found to be 42%-44%, with less than 2.5% variation, which indicates the high reproducibility of the measurement. MTI was then applied to an animal model of white matter disease, acute experimental allergic encephalomyelitis (EAE). In this model of EAE, pathologically proved lesions were edematous with essentially no demyelination. MTRs decreased slightly but significantly (5%-8%) compared with the MTRs of the same tissue region measured before the onset of the lesion [corrected]. Fifteen patients with multiple sclerosis (MS) also underwent MTI. In the 15 patients with MS, all lesions (209 plaques) had a significantly decreased MTR (average, 26%). The authors believe that demyelination produced the lower MTR, and, thus, lesions varied in transfer ratio on the basis of the extent of myelin loss. In patients with MS, particularly those with chronic and/or progressive MS, the MTR of the normal-appearing white matter was significantly decreased. The data suggest that calculated MTR obtained with in vivo MTI may enable differentiation of edema from demyelination, and that MTI can demonstrate white matter abnormalities that cannot be seen with standard spin-echo or gradient-echo magnetic resonance imaging.