Structural brain abnormalities have been observed in adolescents with alcohol use disorders but less is known about neuropathological brain characteristics of teens with sub-diagnostic binge drinking or the common pattern of binge drinking combined with marijuana use. The goal of this study was to examine white matter integrity in adolescents with histories of binge drinking and marijuana use. Diffusion tensor imaging (DTI) was conducted with 42 adolescents (ages 16-19) classified as controls, binge drinkers, or binge drinkers who are also heavy marijuana users. Tract based spatial analysis identified shared fiber structure across individuals and facilitated voxelwise comparisons of fractional anisotropy (FA) and mean diffusivity (MD) between groups. Significant between group differences were found in FA in eight white matter regions (ps < or = .016) between the binge drink-only group and controls, including superior corona radiata, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. Interestingly, in 4 of these same regions, binge drinkers who are also heavy marijuana users had higher FA than binge drinkers who did not use marijuana (ps<.05). MD did not differ between groups. Findings are largely consistent with research suggesting less neuropathology in adolescents without histories of substance use. However, binge drinkers who also use marijuana did not show as consistent a divergence from non-users as did the binge drink-only group. Detection of white matter alterations may have implications in identifying early cognitive dysfunction in substance using adolescents.