The precise characterization of cortical connectivity is important for the understanding of brain morphological and functional organization. Such connectivity is conveyed by specific pathways or tracts in the white matter. Diffusion-weighted magnetic resonance imaging detects the diffusivity of water molecules in three dimensions. Diffusivity is anisotropic in oriented tissues such as fiber tracts. In the present study, we used this method to map (in terms of orientation, location, and size) the "stem" (compact portion) of the principal association, projection, and commissural white matter pathways of the human brain in vivo, in 3 normal subjects. In addition, its use in clinical neurology is illustrated in a patient with left inferior parietal lobule embolic infarction in whom a significant reduction in relative size of the stem of the left superior longitudinal fasciculus was observed. This represents an important method for the characterization of major association pathways in the living human that are not discernible by conventional magnetic resonance imaging. In the clinical domain, this method will have a potential impact on the understanding of the diseases that involve white matter such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, head injury, and spinal cord injury.