PURPOSE: Individuals with Down syndrome (DS) exhibit autonomic dysfunction, manifested as attenuated heart rate (HR) and blood pressure (BP) responses to sympathoexcitation. Whether a subgroup of individuals with DS with a normal HR response would have normal autonomic responses to sympathoexcitation remains unclear. METHODS: We compared autonomic modulation using HR variability (HRV) and BP responses in individuals with and without DS (controls) matched for the HR change to isometric handgrip (HG) (10 DS, 8 controls) and submaximal cycling exercise (CE) (9 DS, 9 controls). HG was performed for 2 min at 30 % of maximal voluntary contraction. CE included two 6-min stages at 0 W and at 50 % of body weight. Beat-to-beat HR and BP were recorded. HRV variables were natural log transformation (Ln) of low frequency (LF), high frequency (HF), LF/HF ratio, total power (TP), and the root mean square of successive differences (RMSSD). RESULTS: In the HG study, although individuals with DS exhibited an overall lower systolic BP, LF/HF ratio, and LnLF/LnHF, their BP and HRV responses to HG were similar to those of the controls. In the CE study, individuals with DS exhibited lower resting LnLF and an overall lower systolic BP and mean arterial pressure compared with controls. During the CE, individuals with DS exhibited an increased diastolic BP and a smaller reduction in LnTP than controls. These differences disappeared after controlling for confounders. CONCLUSIONS: Our results suggest that despite normal HR responses to sympathoexcitatory tasks, HRV was largely similar to controls, with some evidence of autonomic dysfunction in individuals with DS.