The Simons Simplex Collection (SSC) is a unique, rigorously characterized sample of 2,700 families, designed to enrich the discovery of rare de novo events in autism spectrum disorders. Thirteen sites in North America recruited families who have only one child, between 4 and 18 years of age, with an autism spectrum disorder, and unaffected siblings and unaffected biological parents. Individuals with fragile X syndrome, Down syndrome, prematurity, neonatal complications and families with a history of psychiatric disorders are excluded. A detailed medical history was collected and extensive efforts and protocols ensured reliability in administration and scoring of the numerous assessments. Blood samples from all family members were sent to the Rutgers Cell and DNA Repository, genomic DNA was extracted and lymphoblastoid cell lines established and stored. Biospecimens, phenotypic and genotypic data are available to approved researchers via SFARI Base. More than 80 investigators have studies underway which have so far led to nine publications.