To investigate the correlation between water content (WC) and magnetization transfer ratio (MTR) in normal and multiple sclerosis (MS) brain. The MTR has been proposed as a marker for myelin in central nervous system tissue. However, changes in WC due to inflammation and edema may also affect the MTR. Seven MS subjects with active disease and seven age- and gender-matched controls were scanned using quantitative magnetic resonance techniques. WC, myelin water content, T(1) relaxation time, and MTR were calculated from areas of lesion (divided into new lesions less than 2 months old, isointense T(1) lesions, and hypointense T(1) lesions), contralateral normal-appearing white matter (NAWM), and location-matched normal white matter (NWM) in controls. Linear regression was used to determine the correlation between WC and MTR. A significant correlation was found between WC and MTR across all tissue (R = -0.65, P < 0.0005). MTR was correlated with WC in MS tissue, indicating that inflammation and edema influence MTR. Therefore, caution should be used when associating MTR exclusively with myelin content.