Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of the mean diffusivity (MD) and fractional anisotropy (FA) were performed in the NAWM. Correlations between diffusion indices and the full-scale intelligence quotient (FSIQ) and normalized lesion volume were also investigated. Compared with controls, both histogram and ROI analyses showed significant (P less than 0.05) increased MD and decreased FA in the NAWM of TSC patients. In TSC patients, some of the histogram- and ROI-derived diffusion indices of the NAWM were correlated with FSIQ (P less than 0.01), but none of them were correlated with the normalized lesion volume. These findings indicate that TSC patients have occult damage in the NAWM, which might be an important neural basis for intellectual disability in these patients. (Contains 4 figures and 3 tables.)