Objective: We have investigated whether central activation failure (CAF) is in creased during local muscle fatigue in chronic fatigue syndrome (CFS). Methods: Fourteen female CFS patients and 14 age matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle . Before, during, and after sustained MVC, electrical endplate stimulation was a pplied. Force and 5 channel surface EMG (sEMG) were registered. Results: Althoug h force responses upon stimulation during rest did not differ between patients a nd controls, MVC was significantly lower in patients. Already at the beginning o f sustained MVC, CFS patients showed significantly larger CAF than controls (36. 5±17.0%and 12.9±13.3%, respectively). For all individual patients mean CAF o ver the first 45 s was higher than 30%, while it was below 30%for all controls . Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction. Conclusions: Central activation is diminished in CFS patient s. Possible causes include changed perception, impaired concentration, reduced e ffort and physiologically defined changes, e.g. in the corti cospinal excitabil ity or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue. Significance: CFS patien ts show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined. Objective: We have investigated whether central activation failure (CAF) is in creased during local muscle fatigue in chronic fatigue syndrome (CFS). Methods: Fourteen female CFS patients and 14 age matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC ), of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was a pplied. Force and 5 channel surface EMG (sEMG) were registered. Results: Althoug h force responses upon stimulation during rest did not differ between patients Already at the beginning of sustained MVC, CFS patients had significantly more CAF than controls (36.5 ± 17.0% and 12.9 ± 13.3%, respectively). For all individual patients mean CAF o ver the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fiber conduction velocity and the diff Ences between force responses before and after contraction. Conclusions: Central activation is diminished in CFS patient s. Possible causes include changed perception, impaired concentration, reduced e ffort and physiologically defined changes, eg in the corti cospinal excitabil ity or the concentration of neurotransmitters. As a consequence, demands on the muscles are lower, resulting in less peripheral fatigue. Significance: CFS patien ts show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.