The objective of this study was to determine whether subjects with congenital central hypoventilation syndrome (CCHS) had an increased frequency of cardiac arrhythmias and decreased heart rate variability when compared to subjects without a known deficit in control of breathing, and that these abnormalities would be exaggerated by anesthesia. Continuous ambulatory Holter recordings were obtained in patients with CCHS and compared to two otherwise healthy control groups without a deficit in control of breathing: one with an intact airway (n = 11) and a second group with a tracheostomy (n = 6). Holter recordings were obtained before, during (under general anesthesia), and after bronchoscopy. Fourteen children with CCHS (age: 9.3 +/- 4.4 years mean +/- S.D.) were studied, and 7 underwent bronchoscopy. Seventeen control children were studied (age 6.6 +/- 3.6 years): 11 without a tracheostomy, and 6 with a tracheostomy who also underwent bronchoscopy. Maximum heart rate during baseline recording was significantly lower in the CCHS subjects as compared to controls (P = 0.0001). At baseline the difference in the number of arrhythmias/24 hr/subject in all CCHS vs. all control subjects was significant (P = 0.0002); for the subjects who had bronchoscopy, CCHS vs. control, the difference was also significant (P = 0.03). In addition, there was a significant decrease in the number of events/24 hr/subject among the CCHS subjects between baseline and post-bronchoscopy (P = 0.0288). The predominant arrhythmias were sinus bradycardia and transient asystole. The longest asystole in a CCHS subject was 6.50 sec, and in a control subject, 1.42 sec (at baseline the means of the longest asystole were 2.69 +/- 1.4 vs. 1.24 +/- 0.13; P = 0.003 in the CCHS vs. control groups). Other indices of heart rate variability were significantly reduced in the CCHS subjects (P < 0.05). These results substantiate our hypothesis that subjects with CCHS have more arrhythmias than controls, an increased frequency of bradyarrhythmias, and decreased cyclical sinus arrhythmia.