DESCRIPTION (Applicant's abstract): This is a resubmission of an R29 proposal that has been extensively revised. Despite the increasing recognition that children with attention deficit hyperactivity disorder (ADHD) commonly grow up to be adults with the same disorder, little is known about the treatment of this disorder in adults. There are five unanswered questions regarding the MPH treatment of ADHD adults: 1) what is the efficacy of robust MPH therapy (i.e., doses of up to 1.0 mg/kg/day) in ADHD adults diagnosed using DSM-IV, combined type criteria?, 2) what is the medium-term response of ADHD adults to MPH?, 3) what is the safety and tolerability of MPH treatment over the medium-term 4) can MPH-associated improvements in ADHD symptomatology be sustained without MPH after 6 months of effective treatment in ADHD adults ?, and 5) will MPH-associated improvements in ADHD symptomatology translate into improved functional capacities (neuropsychological, social and occupational) as well as increased quality of life after 6 months of effective treatment 7 To this end, the applicant proposes a double-blind, placebo- controlled, study to evaluate the efficacy and tolerability of MPH using daily doses of up to 1.0 mg/kg/day in the treatment of adults with the DSM-IV diagnosis of ADHD of childhood-onset. Careful diagnostic-assessment methods and clinically meaningful doses will be used and the effects on measures of function will be examined. Specific hypotheses will be examined in each of three phases of a double-blind, placebo-controlled, parallel study design. Phase I of the study will consist of a six week assessment of efficacy. During Phase II; subjects who respond in Phase I will be assessed every four weeks for six months. In Phase III, half of the MPH subjects will have their medication discontinued blindly over a four week period and half will remain on their dose of methylphenidate. The double-blind will be maintained throughout each Phase of the protocol. The study will include 150 subjects with the diagnosis of ADHD assessed using the module on ADHD derived from the Kiddie- Schedule for Affective Disorders and Schizophrenia and that of comorbid disorders using the Structured Clinical Interview for adult disorders. Diagnostic and symptom specific rating scales based on DSM-IV will also be used. The ADHD Rating Scale and the Clinical Global Impression Scale will be used to assess global severity and improvement of ADHD symptomatology. Psychosocial functioning and Quality of Life also will be assessed. The auditory and visual continuous performance tasks and the Stroop test will be used to further assess treatment efficacy. A larger neuropsychological battery will be used to assess the long term effects of MPH treatment.