Objective: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS).Methods: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman's test) and Mann-Whitney U-tests for intra- and inter-group comparisons respectively.Results: Mean endurance time for the CFS group was lower (13.1 +/- 3.2 min, mean +/- SEM) than controls (18.6 +/- 2.6 min, P <0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects.Conclusion: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.