PURPOSE: To determine any evidence of damage in normal-appearing white matter (NAWM) tracts in multiple sclerosis (MS) cases using diffusion tensor imaging (DTI). MATERIALS AND METHODS: We retrospectively analyzed anisotropy maps derived from DTI studies performed in 16 MS patients and 14 normal controls. Fractional anisotropy (FA) was measured in NAWM tracts: in the genu and splenium of the corpus callosum and at three points along the corticospinal tracts (internal capsule, cerebral peduncle, and pons). In addition, we performed lesion loads using the manual tracing method in the anterior, posterior, corona radiata, and supratentorial of each side. A FA in NAWM tracts was compared between patients and normal controls using the Student t-test. The FA values and lesion load were compared by performing a Spearman rank correlation. RESULTS: The mean FA values were lower in patients than the controls for the combined genu and splenium (p<0.0001), internal capsule (p=0.03), and cerebral peduncle (p=0.02). Moderate inverse correlations were found between the corpus callosum and the connecting lesion loads (r = -0.40, p = 0.02 for the genu and r=-0.63, p = 0.01 for the splenium). No correlation was found between the FA of the corticospinal tracts and any of the lesion load measurements. CONCLUSION: We found a statistically significant reduction in the FA values when comparing NAWM tracts from patients with MS those in the normal control group. However, only those in the corpus callosum corresponded with plaque burden. NAWM tract deterioration in the corpus callosum and the corticospinal tracts are likely attributed to several concerted pathologic mechanisms as well as Wallerian degeneration.