Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. Twenty children aged 3-17 yr referred for investigation of sleep-disordered breathing (10 DS, and 10 OSA controls) matched for age and obstructive apnea/hypopnea index underwent routine overnight polysomnography. In addition, 10 nonsnoring controls from the general community were studied. Beat-by-beat HR was analyzed from 15 s pre- to 15 s post-spontaneous arousals and compared between groups using two-way ANOVA with repeated measures. Data are presented as means + or - SE. For both rapid eye movement (REM) and non-REM (NREM), arousals were associated with a significant increase in HR in all groups (peak response NREM: DS, 118 + or - 1% at 3 s; OSA controls, 124 + or - 2% at 4 s; and healthy controls, 125 + or - 3% at 4 s; and peak response REM: DS, 116 + or - 2% at 4 s; OSA controls, 123 + or - 3% at 4 s; and healthy controls, 125 + or - 4 at 4 s; P < 0.001 for all). Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P < 0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.