Summary To ascertain whether fatigue perception is tinked to exertion dyspnea and/or to an impaired cardiorespiratory response during watk, 11 patients (8 femates, age range 21 46 years) with muttipte sclerosis (MS) and mitd disabitity underwent the 6-min watk test. Ten healthy subjects (7 females, age range 25 49 years) were studied, as a control group. Patients did not differ from controts in spirometry lung volumes and respiratory muscle strength. There was a significant difference in watk distance between patients and controts (P<0.001), but not in dyspnea percept'ion. ln patients, the watk distance significantly related to d'isabitity score (P<0.01 ), but not to fatigue. Compared to controts, patients had a significant decrease in oxygen putse during watk (P<0.05) and a significant increase in the ventilatory equivalent of CO2 both at basetine and during walk (P<0.05). The retative contribution of both the tidat votume and of the ratio of inspiratory to total breathing cycle duration to the increase in minute ventitation during watk was significantly less in patients, as compared to controts (P<0.05). We conctude that in MS patients with mitd disabitity, fatigue and exertion dyspnea are different sensations without any link and a peripheral limitation during watk can occur. @ 2004 Elsevier Ltd. Att rights reserved.