This is a multi-site collaborative research project from The Research Units on Pediatric Psychopharmacology [RUPP] Autism Network (Indiana University, Seattle Children's Research Institute, UCLA, and Yale University). Recent data indicate that as many as 50% of children with pervasive developmental disorders (PDDs) have moderate to severe problems of hyperactivity and impulsiveness. Consensus is lacking on how to treat children with PDD accompanied by hyperactivity. Compared to typically developing children with ADHD, children with PDD often show less benefit and greater side effect burden. Guanfacine is commonly used in this population, but poorly studied. Pilot data indicate that guanfacine is a promising treatment for hyperactivity in children with PDD with a good tolerability profile. In addition, biomarkers have been identified (genetic and neurochemical) that may be associated with positive effects. This study involves an 8-week randomized, double-blind, placebo- controlled trial of guanfacine for 170 children (ages 5-13 years) with PDD accompanied by hyperactivity and impulsiveness. Subjects who show a positive response will be invited to enter an 8-week Extension phase (treatment mask will not be broken). The treatment blind will be broken for children who do not achieve a positive response in the double-blind phase. Children who show no change or deterioration on placebo will be treated with guanfacine in an 8-week Open-label phase. Children who show a partial response to guanfacine will be randomly assigned to a 4-week add-on trial of methylphenidate or placebo to evaluate the potential benefits of combined treatment. Fifty subjects are expected to enter this pilot trial. The role of gene variants and urinary adrenergic/noradrenergic measures as biomarkers in moderating response to guanfacine on primary efficacy measures and adverse effects will also be explored.