Patients (n = 47) presenting to a neurological centre with unexplained chronic "postviral" fatigue (CFS) were studied prospectively. Controls were patients with peripheral fatiguing neuromuscular diseases and inpatients with major depression in a psychiatric hospital. Seventy-two percent of the CFS patients were cases of psychiatric disorder, using criteria that excluded fatigue as a symptom, compared with 36% of the neuromuscular group. There was no difference in subjective complaints of physical fatigue between all groups. Mental fatigue and fatigability was equally common in CFS and affective patients, but only occurred in those neuromuscular patients who were also cases of psychiatric disorder. Overall, the CFS patients more closely resembled the affective than the neuromuscular patients. Attribution of symptoms to physical rather than psychological causes was the principal difference between matched CFS and psychiatric controls. The symptoms of "postviral" fatigue had little ability to discriminate between CFS and affective disorder. The fatigue in CFS appeared central in origin, suggesting it is not primarily a neuromuscular illness. The implications for research and treatment of chronic fatigue are discussed.