BACKGROUND: The aim of the study was to assess the impairment of the selected white matter tracts within normal appearing white matter (NAWM) in multiple sclerosis (MS) patients using diffusion tensor imaging (DTI). MATERIAL AND METHODS: Thirty-six patients (mean age 33.4 yrs) with clinically definite, relapsing-remitting MS and mild disability (EDSS - Expanded Disability Status Scale 1-3.5) and 16 control subjects (mean age 34.4 yrs) were enrolled in the study. DTI examinations were performed on a 1.5T MR scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained with a small ROI method in several white matter tracts within NAWM including: the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFOF), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of the internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). There were no demyelinative lesions within the ROIs in any of the patients. RESULTS: A significant decrease in FA was found in MS patients in both the ILFs and IFOFs (p<0.001) and in the left MCP and right SLF (p<0.05), compared to the normal subjects. There were no significant differences in FA values in the remaining evaluated ROIs, between MS patients and the control group. A significant increase in ADC (p<0.05) was found only in the right PLIC and the right SLF in MS subjects, compared to the control group. CONCLUSIONS: The FA values could be a noninvasive neuroimaging biomarker for assessing the microstructural changes within NAWM tracts in MS patients.