BACKGROUND AND PURPOSE: After an early progression of signal intensity changes in T2-weighted MR images, also known as "neurofibromatosis bright objects," in patients with neurofibromatosis type 1 (NF-1), there is a tendency toward regression or even disappearance in early adulthood. The purpose of this study was to investigate whether adult patients with NF-1 exhibit generalized microstructural alterations even in normal-appearing brain regions. MATERIALS AND METHODS: Conventional and diffusion tensor MR imaging of the brain was obtained in 10 adult patients with NF-1 and 10 age-matched healthy volunteers. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain stem, basal ganglia, thalamus, corpus callosum, and frontal and parietooccipital white matter regions. RESULTS: Significantly increased ADC and decreased FA values were found in all regions of interest and in all patients with NF-1, irrespective of their scholastic achievement and subsequent professional performance, compared with control subjects (P < .001). There were no significant correlations with the age (P > .1) or with the lateralization between brain hemispheres (P > .05). CONCLUSION: Diffusion tensor imaging reveals globally elevated FA and decreased ADC values in the mature brains of patients with NF-1, which is most likely a consequence of diffuse and basic alterations in cerebral microstructure that result from the underlying gene mutation.