This within-family study investigated whether mothers differentiate between children in their interactive behavior. Mothers were observed during a play and a task interaction separately with their child with autism spectrum disorder (ASD) (between 46 and 84 months old, M = 68) and with a younger sibling (between 29 and 67 months old, M = 48). Additionally, the social behavior of the children with ASD and their non-ASD siblings was compared. Results show that mothers differentiated in their responsiveness but not in their initiatives toward the children. Children with ASD and their non-ASD siblings were equally responsive but children with ASD were more imperative toward their caregiver. Several interpretations of these findings are discussed. Finally, it is concluded that family-based interventions will benefit from a better understanding of the effect of ASD on mother–child interactions within families with a child with ASD. Therefore, between-family studies should be complemented with within-family studies. Autism Res2011,4:358–367. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.