Improving the understanding of gene-environment interaction (GxE) as a causative factor in autism has been identified as a research priority in the NIH Interagency Autism Coordinating Committee's (IACC's) Strategic Plan for Autism Spectrum Disorders (ASD) Research as well as in the IOM's Report on Autism and the Environment. However, empirical investigations of GxE in autism remain scarce. The Study to Explore Early Development (SEED) is a multisite ASD case-control investigation recruiting 900 3-5 year old children with ASDs, 900 typically developing controls, and 900 children with non-autism developmental impairments. This grant will support research on a subset of SEED participants, including 500 autism cases and 500 controls to identify genes whose effects on ASD may vary across environmental exposure categories related to pre-natal infection, maternal medication use, or smoking and drinking during pregnancy. This work will accelerate future efforts centered around gene-environment interaction both in the full set of SEED participants and in other data sets for autism.