Previous studies have shown decreased voluntary muscle strength and endurance in patients with fibromyalgia. The aim of this study was to determine to what extent this is due to lack of exertion. The twitch interpolation technique was used to determine the degree of central activation and estimate the "true" quadriceps muscle strength in patients with fibromyalgia and age and sex matched controls. Subjects hereafter performed an endurance test consisting of repetitive contractions at 50% of estimated "true" muscle strength of four seconds duration followed by a six second rest until exhaustion, or maximally for 40 minutes. Twitch decline and increases in mean rectified EMG were used as objective markers of fatigue. The estimated "true" muscle strength was 82 (SD 26) Nm in 20 patients with fibromyalgia compared with 133 Nm (SD 28) Nm in the 21 controls (p < 0.001). The "true" muscle strength per cm2 midthigh cross sectional area was lower 0.50 (SD 0.15) Nm/cm2 in the patients compared with 0.74 (SD 0.15) Nm/cm2 in the controls (p < 0.001). The decline over time in twitch sizes was similar in the two groups. The mean rectified EMG signal at a fixed force level of 50% of "true" muscle strength increased similarly in the two groups. Relaxation rates and contraction rates also increased equally in the two groups. In conclusion, a reduction of the estimated muscle strength per area unit of about 35% was found in the patients with fibromyalgia. This might be secondary to physical inactivity or neuroendocrine factors. No differences in changes in the neurophysiological indices associated with fatigue were found between the two groups.