Objective: To determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression. Method: Subjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.).Outcomes were global improvement in ADHD and depression (clinicianrated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated). Results: Clinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHU only. Compared with post-placebo ratings, final parents' (p <.0005) and children's (p =.016) ratings of depressive symptomatology improved significantly, as did parents' (p <.0005) but not teachers' (p =.080) ratings of ADHD symptomatology. Final ratings of functional impairment improved significantly from enrollment (p <.0005). No subject discontinued medication because of side effects. Conclusions: Bupropion SR may be effective and well-tolerated in adolescents with comorbid ADHD and depressive disorders. However, randomized, placebo-controlled studies are needed.