To assess the involvement of basal ganglia and thalamus in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI) method. Fourteen definite-ALS patients and 12 age-matched controls underwent whole brain DTI on a 3T scanner. Mean-diffusivity (MD) and fractional anisotropy (FA) were obtained bilaterally from the basal ganglia and thalamus in the regions-of-interest (ROIs). The MD was significantly higher (P < .02) in basal ganglia and thalamus in patients with ALS compared with controls. Correspondingly, the FA was significantly lower (P < .02) in these structures, except in caudate (P = .04) and putamen (P = .06) in patients compared with controls. There were mild to strong correlations (r = .3-.7) between the DTI measures of basal ganglia and finger-tap, foot-tap, and lip-and-tongue movement rate. The increased MD in basal ganglia and thalamus and decreased FA in globus pallidus and thalamus are indicative of neuronal loss or dysfunction in these structures. Copyright © 2012 by the American Society of Neuroimaging.