Pulmonary functions at rest and cardiorespiratory responses to low speed treadmill walking were investigated in 24 patients (P), (mean age, 38 years; range, 20 to 56 yr) with multiple sclerosis and compared with a control group (C). The following parameters were significantly (p < 0.01) different in P from those in C. At rest in P, the residual volume to TLC ratio was 21% greater, respiratory muscle strength index was 28% lower, and heart rate (HR) was 11 beats/min−1 higher. During treadmill walking at a given speed, HR, minute ventilation , and O2 consumption were all elevated (37 to 119%). In addition, the energy cost of walking, per unit distance, above resting, was 2 to 3 times greater, with mean ± SEM values for P of 0.299 ± 0.019 and C of 0.147 ± 0.006 at 2 km/h and 0.275 ± 0.042 and 0.110 ± 0.005 (for P and C, respectively) ml O1 kg−1m−1 at 4 km/h; the HR and , also when referred to a given , were higher. We conclude that a high energy cost of walking may be an important contributing factor to breathlessness and leg fatigue in patients with multiple sclerosis. Poor conditioning, altered cardiovascular control, and respiratory muscle weakness may play additional roles.