Fatigue is a common symptom but guidelines for its appropriate evaluation are lacking. The authors prospectively studied 100 adults with a chief complaint of fatigue lasting at least 1 month in order to determine the diagnostic contribution of physical examinations and laboratory investigations. The evaluations were performed in the specialized clinic of a faculty practice. Physical examinations produced diagnostic information in 2% of patients, and laboratory investigations elucidated the cause of fatigue in 5% of patients. Structured follow-up evaluations after an average interval of 10 months failed to reveal any new organic causes for the fatigue symptom. Minor laboratory abnormalities were relatively common but did not contribute to the diagnostic process and did not seem to influence the clinical outcome. The authors conclude that the traditional medical evaluation of patients complaining of chronic fatigue has a low yield in discovering treatable physical disorders.