Abnormal fatigue is a common symptom in persons with multiple sclerosis (MS). In MS patients complaining of this symptomatic fatigue, it has been suggested that impaired cardiovascular function may contribute to the pathogenesis of muscle fatigue in MS. PURPOSE To determine if decreased muscle endurance in persons with MS who report symptomatic fatigue is blood flow related. METHODS Eight MS (4 f, 4 m, median EDSS = 4); and 7 age-matched control (C) subjects (4 f, 3 m) performed fatiguing isometric dorsiflexion exercise with and without arterial occlusion (suprasystolic thigh cuff inflation) of the lower leg. On the initial visit, symptomatic fatigue was measured by the Fatigue Impact Scale (FIS) and the Fatigue Severity Scale (FSS). Testing occurred on separate days separated by at least 48 hrs and was counter-balanced in a random fashion. Exercise intensity was 45% of initial maximal voluntary contraction (MVC), with a 75% duty cycle (6s contract, 2s relax), until task failure. MVC was obtained initially and immediately after task failure. Endurance time (ET) was the time to task failure. Fatigue was indicated by the post-exercise MVC to pre-exercise MVC ratio expressed as percent. RESULTS Results are mean ± SE. MS and control subjects were of similar age (MS = 48 ± 8 yrs, C = 42 ± 7 yrs). MS compared to C subjects reported more symptomatic fatigue with both FIS (MS = 62 ± 17, C = 1 ± 1, p<0.01) and FSS (MS = 4.5 ± 0.5, C = 1.7 ± 0.2, p<0.01). In exercise with occlusion, there was no difference between groups in ET (MS = 214 ± 29s, C = 227 ± 30s) or muscle fatigue (MS = 45 ± 5%, C = 40 ± 4%). In exercise without occlusion, ET was shorter in MS compared to C groups (MS = 303 ± 53s, C = 559 ± 30s, p<0.05). However, muscle fatigue (MS = 67 ± 6%, C = 62 ± 4%) was similar between groups. CONCLUSIONS When any effect of blood flow, or oxygen delivery, was removed during occlusion, ET was similar between groups. Because ET was shorter in MS compared to C when circulation was intact, we conclude that impaired blood flow (i.e., oxygen delivery) or oxygen usage during exercise in MS may be associated with decreased muscle endurance. Sponsored by the National Multiple Sclerosis Society.