The authors examined the efficacy of methylphenidate (MPH) and lithium to treat attention-deficit/ hyperactivity disorder (ADHD) in adults, using a randomized, double-blind, crossover design. Patients received 8 weeks of MPH treatment (up to 40 mg/day) and 8 weeks of lithium treatment (up to 1,200 mg/day), by random assignment. Independent evaluators blind to group assignment assessed response every 2 weeks and at the end of each phase. The primary outcome measure was the Conners' Adult ADHD Rating Scale sum score for the clusters of hyperactivity, impulsivity, and learning problems. Secondary outcome measures were scores of irritability, overt aggression, antisocial behavior, anxiety, and depression, and scores on tests of verbal learning and sustained attention. In this preliminary study, lithium and MPH produced similar improvements on the primary outcome measure and on measures of irritability, aggressive outbursts, antisocial behavior, anxiety, and depression.