The National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Child Health and Human Development (NICHD) have entered into a public-private partnership with the Canadian Institutes of Health Research (CIHR), the Health Research Board, Ireland (HRB), Cure Autism Now (CAN), the National Alliance for Autism Research (NAAR), Autism Speaks and the FRAXA Research Foundation (FRAXA) to jointly sponsor this Funding Opportunity Announcement (FOA), which is aimed at characterizing, understanding and treating etiological and pathophysiological mechanisms common to both Fragile X syndrome (FXS) and autism (including autism spectrum disorders such as Rett syndrome). Between 2.5% and 6% of individuals with autistic feature have FXS, and approximately 15% to 25% of children with FXS have autism. An additional 50% to 90% of children with FXS exhibit some symptoms and features associated with autism, including poor eye contact, hand flapping, hand biting, speech perseveration and other language abnormalities and problems, as well as tactile defensiveness, mental retardation in the moderate to severe range, developmental delay, sensory hyperarousal, and social anxiety with mood liability. Researchers have argued that autism and autistic symptoms in FXS reflect a common etiological or pathophysiological pathway underlying the two conditions. Ongoing basic neuroscience research on FXS in model systems like the mouse and fly are providing a wealth of information at multiple levels – subcellular, cellular, and intercellular networks or circuits – to delineate the neurobiology of this disorder. These studies should dissect components of the neurobiology of autism, especially in patients with both FXS and autism, and identify novel targets for new drugs to treat both disorders. Applications submitted in response to this FOA should focus on a topic related to understanding neural pathways, circuits, systems and molecules that play a role in the etiology or pathophysiology of FXS and may be implicated in autism (including autism spectrum disorders such as Rett syndrome). Studies emphasizing the identification of drug targets for new therapeutic drugs to treat FXS and autism are particularly encouraged. Research projects supported under this FOA that include human subjects should include children affected with both FXS and autism and animal studies may include several models systems, e.g., mouse, fly and zebrafish. Basic neuroscience research in model systems should focus on both FXS and autism.