Objective. To determine if task performance and fatiguability during repeated low-level contractions of an intrinsic hand muscle differ in a group of MS subjects compared with a control group, and what central changes accompany the development of fatigue and the period of recovery, whether these measures are related to subjective ratings of fatigue or perception of effort. Methods Force of index finger abduction, rating of perceived effort, and motor evoked potential amplitude and silent period duration were measured during and after a 20-min. intermittent submaximal (40%) contraction of the first dorsal interosseous muscle in 23 clinically definite MS subjects with mild-moderate symptoms, and 15 controls. Results Rating of perceived effort increased at a greater rate in the MS group than in control subjects during exercise, and this was associated with larger increases in both MEP amplitude and silent period duration. Conclusions Submaximal fatiguing exercise is associated with an enhanced central motor drive and increased perception of effort in MS. Significance MS subjects can increase central drive during fatiguing exercise to a greater degree than controls, but this is associated with greater perceived exertion. These factors may underlie the more general complaint of fatigue experienced by people with MS.