Objectives-Patients with chronic fatigue syndrome complain of physical and mental fatigue that is worsened by exertion. It was predicted that the cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would diVer from those in depressed and healthy controls. Methods-Ten patients with chronic fatigue syndrome, 10 with depressive illness, and 10 healthy controls completed cognitive and muscle strength testing before and after a treadmill exercise test. Measures of cardiovascular functioning and perceived eVort, fatigue, and mood were taken during each stage of testing. Results-Depressed patients performed worst on cognitive tests at baseline. During the treadmill test, patients with chronic fatigue syndrome had higher ratings of perceived eVort and fatigue than both control groups, whereas patients with depression reported lower mood. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused (p=0.02) and sustained (p=0.001) attention, as well as greater deterioration than depressed patients on the focused attention task (p=0.03). No between group diVerences were found in cardiovascular or symptom measures taken during the cognitive testing. Conclusions-Patients with chronic fatigue syndrome show a specific sensitivity to the eVects of exertion on eVortful cognitive functioning. This occurs despite subjective and objective evidence of eVort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both. Further insight into the pathophysiology of the core complaints in chronic fatigue syndrome is likely to be realised by studying the eVects of exercise on other aspects of everyday functioning. (J Neurol Neurosurg Psychiatry 1998;65:541-546)