BACKGROUND We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). METHODS This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome. RESULTS Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001). CONCLUSIONS Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.