This article presents results of a randomized controlled trial examining the efficacy of Parent-Child Interaction Therapy (PCIT) for treating disruptive behaviors of young children (ages 3 to 6) with mental retardation (MR) and comorbid oppositional defiant disorder. Thirty families were randomly assigned to an immediate treatment (IT) or waitlist (WL) control group. Results indicated that IT mothers interacted more positively with their children after treatment than WL mothers, and their children were more compliant after treatment. On parent-report measures, IT mothers reported fewer disruptive behaviors at home and lower parenting stress related to difficult child behavior than WL mothers after treatment. Whether evidence-based treatments for disruptive behavior require modification before application to children with MR is discussed.