Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood psychiatric disorder, present in between 3 to 10% of children in the United States (Wender et al 2001). It is thought to reflect subtle anomalies in the central nervous system and thus structural neuroimaging has been used extensively to delineate the neurobiology of the disorder. Magnetic resonance imaging has demonstrated structural anomalies in ADHD, affecting all the major lobes with particularly severe volume reductions in the cerebellum and relative preservation of the caudate nucleus (for a review see Durston 2003). In structural neuroimaging work, studies with monozygotic twins who are discordant for the disorder have proved a particularly powerful tool, with findings of a significantly smaller caudate nucleus in the affected twin compared to the unaffected, but genetically identical, twin (Castellanos et al 2003). We have previously reported an overall reduction in white matter volume in all four major brain lobes, with the deficit appearing to be fixed and non-progressive. However, recent advances in neuroimaging of white matter make feasible an examination of white matter characteristics, such as the degree of myelination and the coherence of white matter tracts. The proposed project builds on our anatomic magnetic resonance imaging (MRI) studies that have been performed with a 1.5-Tesla scanner in children who have Attention-Deficit/Hyperactivity Disorder (ADHD) and normal controls. We now propose to use diffusion tensor magnetic resonance imaging (DT-MRI) as conventional T(1)- and T(2)-weighted images at 3-Tesla to visualize and quantify white matter tracts in the brains of normal monozygotic (MZ) twins, MZ twins who are concordant for ADHD, and MZ twins who are discordant for ADHD. Ages will range from 6 to 21 years. Our principal focus will be on development and possible abnormalities of white matter tracts linking prefrontal-striatal-thalamic circuits in which we hypothesize disruption of these tracts in affected twins relative to their healthy co-twins. We will also explore the usefulness of this technique in delineating white matter in cerebellar circuits and characterize the normal development of white matter from ages 6 to 21 by using a single healthy twin per family.