Multiple sclerosis patients with motor involvement of the lower extremities and the trunk often experience exertional dyspnea and generalized or leg fatigue on walking, and their walking performance is reduced. It has recently been suggested that a high energy cost of walking (Cw) may be an important contributing factor to the observed dyspnea and fatigue. The purpose of this study was to determine which factors influence Cw. Clinical tests were used to assess the major alterations of the motor system. Thirty-three patients (mean age 41 years, mean maximal speed 2.8 km/h, range 1.2 to 6.2 km/h) in a stable phase of their disease were examined. Cost of walking (mean +/- SE) at 1.8 km/h was 0.287 +/- 0.018 ml 02.kg-1.m-1 (normal value 0.163 +/- 0.007, p less than 0.001). A multivariate regression analysis showed that Cw was significantly related to spasticity of the lower extremities, whereas lower extremity and truncal weakness did not contribute to the observed high Cw.