Individuals with Down syndrome (DS) exhibit low peak aerobic capacities and heart rates. Although autonomic modulation is attenuated in individuals with DS at rest, the exercise response appears normal. This suggests that mechanisms other than autonomic control influence the low aerobic capacity, such as catecholamine responsiveness to exercise. The purpose of this study was to determine catecholamine responses to a peak treadmill test in a group of subjects with DS compared with a nondisabled group. Epinephrine and norepinephrine concentrations were measured at rest and immediately after graded exercise tests on a treadmill in 20 subjects with DS (mean age, 24 ± 7 years) and 21 nondisabled subjects (mean age, 26 ± 6 years). Catecholamines increased significantly with peak exercise in the control group (p <0.05), with little to no change in subjects with DS. In conclusion, the different catecholamine responses to peak exercise, in particular the lack of a response in individuals with the DS, may be a primary mechanism to explain the reduced peak heart rates and low work capacities observed in this population.