This study determined whether dexamphetamine improved symptoms and quality of life in patients with chronic fatigue syndrome. The setting was a specialized clinic within a tertiary referral hospital. This was a 6-week parallel-group, placebo-controlled trial with random allocation. There was a 2-week dose-adjustment phase and a 4-week stable treatment period. Outcome measures were the Fatigue Severity Scale, the Medical Outcomes Study 36-item Short-Form Health Survey, and two patient-determined outcomes. Ten patients were randomly assigned to dexamphetamine, and 10 were assigned to placebo. Fatigue Severity Scale scores improved in nine of 10 dexamphetamine and four of 10 placebo patients. The change in mean score was statistically significant. There were large but statistically nonsignificant changes in scores for the Short-Form Health Survey domains vitality and physical functioning. Dexamphetamine may be useful in the management of chronic fatigue syndrome; a larger and longer trial is justified by these results.