This study intended to investigate walking economy (WE) in response to different treadmill speeds and grades in adults with Down syndrome (DS) and in non-disabled controls. Eighteen participants (14 males; 4 females) with DS (33.6+/-7.6 years) and 16 non-disabled (12 males, 4 females) controls (33.3+/-8.0 years) performed submaximal (2.5 km . h (-1) and 4 km . h (-1) at 0% grade; 4 km . h (-1) at 2.5% and 5% grade, for 5 min each) and maximal treadmill tests with metabolic and heart rate measurements. Oxygen uptake (VO(2)) was not different between groups at rest or during the slowest treadmill speed. However, at faster speeds and increased grades, adults with DS presented lower WE than controls (p<0.0001). Subsequent analyses revealed that, despite showing higher delta VO(2) response to the selected speed increments (p<0.0001), individuals with DS produced similar VO(2) increase as controls to grade variations. Therefore, adults with DS exhibit lower WE than non-disabled controls at a speed faster than their preferred walking speed. Additionally, in comparison to controls, individuals with DS show a greater change in energy expenditure with a change in walking speed. In conclusion, lower WE in individuals with DS is mainly related to their inability to adapt efficiently to positive variations in walking speed.