Increasing health care costs and disturbing gaps in quality of care make it imperative to identify and implement the most effective and efficient health care services. This need for effectiveness research to guide practice and policy is especially pressing in mental health disorders, including autism, which is common, often devastating, and expensive. The overarching goal of this research is to create a large, comprehensive and dynamic autism spectrum disorder (ASD) registry across several integrated health systems participating in the Mental Health Research Network (MHRN). The MHRN includes nine established public domain research centers based in integrated not-for-profit health systems. These systems provide care to a diverse population of 10 million people in 11 states, and they share rich and compatible data resources to support a range of effectiveness research. Diversity of member demographics, insurance coverage, and organization of health services make this network an ideal environment for studying variation in care, comparing effectiveness and cost of treatments across practice environments, and studying dissemination and health policies. The Autism Registry will enable rapid identification and enrollment of patients into future large-scale comparative effectiveness studies testing treatment, preventive and services interventions, as well as future pharmacogenomic and etiologic investigations. The many unique resources provided by the MHRN will be leveraged in this research, including: 1) the large and ethnically diverse population of children with ASD, who are representative of the communities served by the health plans, 2) comprehensive electronic medical records (EMR) systems which capture all patient interactions with the health plans, 3) existing biospecimen repositories at some participating sites that will facilitate collection of genetic material from children and their family members, and 4) researchers with an established track record of engaging and enrolling patients in autism clinical research studies and extensive experience in conducting research using electronic databases. The Autism Registry will both yield important data regarding diagnosis and management of ASD in a nationwide population-based sample and establish an infrastructure to dramatically accelerate future effectiveness research regarding ASD.