Project Summary The goal of this phase I/II multicenter clinical trial is to improve walking function, dynamic stability, and community mobility in people with multiple sclerosis (MS) using a novel combination of high-intensity training and an environment that challenges dynamic balance. There are two critical elements of this proposal: 1) balance perturbations applied during treadmill walking will allow participants to develop neuromuscular strategies to maintain upright posture, which will be refined and enhanced with repeated practice, and 2) patients who engage in high-intensity training will improve their neuromuscular and cardiorespiratory capacity to facilitate the ability to walk faster and further. Indeed, patients with mild or moderate MS present with altered locomotor and postural control, and this 2X2 factorial design will delineate the individual and combined effects of repeated exposure to postural perturbations during walking and high-intensity exercise that may enhance locomotor and balance control in both laboratory conditions and in the real-world, where the locomotor and postural demands are substantial. This study is predicated on the previous experience of the investigators with high-intensity training in patients with other neurological disorders and promising results of a pilot study demonstrating feasibility of dynamic balance treadmill training in people with MS. The present project will attempt to delineate changes in clinical and laboratory measures of locomotor capacity following walking- specific exercise training at high vs low intensity and with or without postural perturbations during treadmill stepping (Aim 1). Aim 2 will demonstrate the relative efficacy of these strategies on dynamic postural control (i.e., balance) and relate improvements in the response to perturbations to secondary measures of community falls. Finally, Aim 3 will delineate changes in community mobility and participation following these various exercise paradigms. We suggest that high-intensity locomotor training with postural perturbations will elicit the largest changes in both locomotor and balance outcomes, and these combined gains will boost physical activity in the community setting leading to improved quality of life.