Objective: This study investigated the psychometric properties of the Social Communication Questionnaire (SCQ) in a sample of children with Down syndrome (DS), many of whom had a co-occurring autism spectrum disorder (ASD). The SCQ is a widely used ASD screening measure; however, its measurement properties have not been comprehensively evaluated specifically in children with DS, a group that seems to be at higher risk for an ASD. Methods: Exploratory and confirmatory factor analyses, scale reliability, convergent and discriminant correlations, significance tests between groups of children with DS and DS + ASD, and diagnostic accuracy analyses were conducted. Results: Factor analyses identified 2 reliable factors that we labeled Social-Communication and Stereotyped Behavior and Unusual Interests. Pearson correlations with Autism Diagnostic Interview-Revised subscales indicated support for the SCQ's convergent validity and some support for the discriminant validity of the factor-based scales. Significance tests and receiver operating characteristic analyses indicated that children with DS + ASD obtained significantly higher SCQ factor-based and total scores than children with DS alone, and that the SCQ Total Score evidenced good sensitivity and adequate specificity. Conclusions: Results indicated initial psychometric support for the SCQ as an ASD screening measure in children with DS. The SCQ should be considered as part of a multimethod evaluation when screening children with DS.