This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis of HR variability was performed on the last 256 consecutive R-R intervals obtained under the following conditions: (1) rest, (2) submaximal treadmill exercise (at constant relative intensity below the ventilatory threshold) and (3) recovery. Participants with DS presented lower chronotropic response than those without DS to peak and submaximal exercise (p<0.05). Nevertheless, the fractional utilization of peak HR during treadmill walking was similar between groups (∼60% peak HR). Even though there were no between-group differences at rest or during recovery, the participants with DS showed a higher LF/HF ratio during exercise (p<0.05). Similarly, the LF power of participants with DS during exercise was greater than that of nondisabled participants (p<0.05). In contrast, both groups exhibited similar HF power at each physiological condition. In conclusion, these findings suggest that adults with DS demonstrate appropriate vagal withdrawal, but heightened sympathetic modulation of HR variability at ∼60% of their peak HR. Despite this, the absolute change in HR from rest to exercise was attenuated in these individuals compared to persons without disabilities. This indicates that DS may be associated with poor cardiac responsiveness to changes in autonomic modulation during exercise at intensities below the ventilatory threshold.