The aim of this study was to differentiate the effects of body load and joint movements on the leg muscle activation pattern during assisted locomotion in spinal man. Stepping movements were induced by a driven gait orthosis (DGO) on a treadmill in patients with complete para-/tetraplegia and, for comparison, in healthy subjects. All subjects were unloaded by 70% of their body weight. EMG of upper and lower leg muscles and joint movements of the DGO of both legs were recorded. In the patients, normal stepping movements and those mainly restricted to the hips (blocked knees) were associated with a pattern of leg muscle EMG activity that corresponded to that of the healthy subjects, but the amplitude was smaller. Locomotor movements restricted to imposed ankle joint movements were followed by no, or only focal EMG responses in the stretched muscles. Unilateral locomotion in the patients was associated with a normal pattern of leg muscle EMG activity restricted to the moving side, while in the healthy subjects a bilateral activation occurred. This indicates that interlimb coordination depends on a supraspinal input. During locomotion with 100% body unloading in healthy subjects and patients, no EMG activity was present. Thus, it can be concluded that afferent input from hip joints, in combination with that from load receptors, plays a crucial role in the generation of locomotor activity in the isolated human spinal cord. This is in line with observations from infant stepping experiments and experiments in cats. Afferent feedback from knee and ankle joints may be involved largely in the control of focal movements.