The aim of this study is to evaluate the reliability, validity and responsiveness of the Dutch version of the Modified Fatigue Impact Scale. Fifty-one randomly selected subjects with definite multiple sclerosis (MS) (mean age 51.9 +/- 10.5 years, 25 women) and 20 healthy controls (mean age 50.6 +/- 14.0 years, 13 women) filled in the Modified Fatigue Impact Scale (MFIS), the Fatigue Severity Scale (FSS) and the fatigue subscale of Guy's Neurological Disability Scale (GNDS). All tests were repeated with an interval of maximum three days. The hospitalised individuals with MS (n = 20) were assessed at intake and discharge. No significant difference was found between first and second administration of MFIS (z = -.519, p = .603, Wilcoxon signed ranks test), with a good correlation (.729). MFIS was able to distinguish individuals with MS from controls, and subjects with fatigue from the non-fatigued group. MFIS showed no floor or ceiling effect. MFIS correlated moderately with Fatigue Severity Scale (.447) and the fatigue subscale of GNDS (.487). The 20 hospitalised subjects had significant lower MFIS scores (z = -3.401, p = .001) after a four-week rehabilitation programme, whereas the FSS did not change. This study indicates that the Dutch version of the MFIS is a reliable, valid and responsive tool to assess the impact of MS-related fatigue on daily life.