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OBJECTIVE--To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. DESIGN--Cohort study. SUBJECTS--139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. SETTING--University hospital referral centre. MAIN OUTCOME MEASURES--Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. RESULTS--65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. CONCLUSION--Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.