To ascertain whether fatigue perception is linked to exertion dyspnea and/or to an impaired cardiorespiratory response during walk, 11 patients (8 females, age range 21-46 years) with multiple sclerosis (MS) and mild disability underwent the 6-min walk test. Ten healthy subjects (7 females, age range 25-49 years) were studied, as a control group. Patients did not differ from controls in spirometry, lung volumes and respiratory muscle strength. There was a significant difference in walk distance between patients and controls (P<0.001), but not in dyspnea perception. In patients, the walk distance significantly related to disability score (P<0.01), but not to fatigue. Compared to controls, patients had a significant decrease in oxygen pulse during walk (P<0.05) and a significant increase in the ventilatory equivalent of CO2 both at baseline and during walk (P<0.05). The relative contribution of both the tidal volume and of the ratio of inspiratory to total breathing cycle duration to the increase in minute ventilation during walk was significantly less in patients, as compared to controls (P<0.05). We conclude that in MS patients with mild disability, fatigue and exertion dyspnea are different sensations without any link and a peripheral limitation during walk can occur.