To examine acute metabolic responses to treadmill locomotion in a participant with motor-complete tetraplegia. The participant--a woman with a chronic ASIA B C3-C4 spinal cord injury--walked on a treadmill with 40% body weight support (BWS) and robotic assistance. Oxygen consumption (VO2), minute ventilation (VE), and heart rate (HR) were measured during seated resting, supported standing, and 40 minutes of walking with stepping assistance from a Lokomat-driven gait orthosis. A resting VO2 equal to 50 milliliters per minute was predictably low, and did not change after the participant assumed an upright posture. Both VO2 and VE increased immediately upon onset of locomotion, suggesting a neurogenic rather than a humoral regulatory response to movement. VO2 averaged 2.4 metabolic units (METS) during locomotion at an average expenditure of 2.98 kilocalories per minute. HR was unaltered by standing, but during locomotion averaged 1 7 beats higher than during resting. Increases in VE but not VO2 upon standing, and decreases in VO2 but not VE immediately after walking, rule out changes in VE alone as the source for increased VO2 during walking. The data collected on this single participant show that treadmill locomotion with BWS and robotic assistance elicits a metabolic response to treadmill gaiting characterized by increased VO2, VE, HR, and caloric expenditure.