The corpus callosum is the largest commissural white matter pathway that connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI) was performed on subject groups with high-functioning autism and controls matched for age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus callosum and subregions (genu, body and splenium) were made and compared between groups. The results showed that there were significant differences in volume, fractional anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences appeared to be driven by a subgroup of the autism group that had small corpus callosum volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had significantly lower performance IQ measures than either the other individuals with autism or the control subjects. Measurements of radial diffusivity also appeared to be correlated with processing speed measured during the performance IQ tests. The subgroup of autism subjects with high mean diffusivity and low fractional anisotropy appeared to cluster with the highest radial diffusivities and slowest processing speeds. These results suggest that the microstructure of the corpus callosum is affected in autism, which may be related to nonverbal cognitive performance.