To assess for the presence of microscopic abnormalities in otherwise normal-appearing white matter on T2-weighted images in patients with multiple sclerosis (MS) by using magnetization-transfer (MT) measurements. Twenty-three patients with MS and nine healthy control subjects underwent magnetic resonance (MR) imaging with a 1.5-T system. MT ratios (MTRs) were measured in 16 areas of normal-appearing white matter identified on conventional T2-weighted images in patients with MS. MTRs in the same white-matter locations in control subjects were determined. The two groups were compared. The mean whole-brain MTR of normal-appearing white matter in patients was 40.13% +/- 1.37 (standard deviation; range, 36.31%-42.09%); in control subjects, 42.93% +/- 0.95 (range, 41.62%-44.50%). The difference was statistically significant (P < or = .001). Except for the internal capsules, the difference in mean MTRs in each sublocation of the brain between patients and control subjects was statistically significant (P < or = .05). MT measurements are more sensitive than conventional MR imaging in the detection of abnormalities beyond the resolution of T2-weighted imaging.