BACKGROUND AND PURPOSE: Prelingual deafness is a hearing loss that occurs before language is acquired and may result in brain structural alterations. We studied microstructural WM alterations in prelingually deaf adolescents by using DTI. We hypothesized that any morphologic alterations are mainly located in the auditory association areas. Furthermore, considering that the developing brain is both more vulnerable to deprivation and more plastic than the adult brain, we speculated that the affected areas should be larger than those previously reported in adult deafness. MATERIALS AND METHODS: Diffusion tensor images were obtained from 16 prelingually deaf adolescents (age range, 10-18 years) and 16 healthy control adolescents matched for age and sex. Both groups were compared in fractional anisotropy and radial diffusivity by tract-based spatial statistics. In addition, we examined the correlation between the structural data (FA, RD) differences and the duration of sign language use and hearing aid experience. RESULTS: Prelingually deaf adolescents had significantly lower FA and increased RD in the bilateral superior temporal gyri, Heschl gyrus, planum polare, and the splenium of the corpus callosum. Only RD values in the right superior temporal gyrus correlated significantly and negatively (r = -0.518; P = .040) with duration of sign language use. These alterations were larger than those previously reported in adult deafness. CONCLUSIONS: As expected, we found severe morphologic changes of decreased FA and increased RD in multiple auditory association areas and in the corpus callosum. These changes are signs of development impairments in prelingually deaf adolescents, possibly reflecting axonal loss or lack of myelination.