The term “autism” is being increasingly recognized as a diagnostic category that covers a large number of, as yet, unidentified brain disorders of childhood onset. In contrast, Fragile X syndrome (FraX) is a common, readily identified genetic condition associated with greatly increased risk for autistic behavior. Thus, FraX offers a unique opportunity to study how genetic and environmental factors lead to autistic behavior, and how disease-specific treatments can reduce such behaviors. Preliminary studies from the research team and others indicate that dysfunction of a specific neurochemical system of the brain (the “cholinergic” system) is relevant to FraX and that intervention to augment this system may have beneficial effects for both behavior and learning. Two objectives are proposed for this research. First, to conduct a controlled clinical trial to assess whether a medicine that increases cholinergic function (donepezil) can reduce autistic behavior and improve cognition in persons with FraX; and second, to use special magnetic resonance imaging (MRI) techniques to assess change in brain function and neurochemistry associated with donepezil treatment. Autistic behaviors occurring in FraX are similar to those observed in idiopathic (non-FraX) autism. Like idiopathic autism, behavioral and learning problems in FraX contribute to impairments in social development, disturbance in the parent-child relationship and educational failure. Accordingly, the study of FraX as a “comprehensible” model for autism has been increasingly proposed. As hypotheses about cholinergic dysfunction have been offered for idiopathic autism as well as FraX, the results of the study hold promise for informing future research in autistic populations who share genetic or neurobiological links to FraX.