Little is known regarding the influence of asthma and exercise, and their interaction, on heart rate variability (HRV) in adolescents. Thirty-one adolescents with asthma (13.7+/-0.9 years; 21.9+/-3.9 kg.m(-2); 19 boys, 12 girls) and thirty-three healthy adolescents (13.8+/-0.9 years; 20.3+/-3.2 kg.m(-2); 16 boys, 17 girls) completed an incremental ramp test and three heavy-intensity constant-work-rate cycle tests. Thirteen adolescents (7 boys, 6 girls; 6 asthma, 7 control) completed six-months high-intensity interval training (HIIT) and were compared to age- and sex-matched controls. Standard time-domain, frequency-domain and non-linear indices of HRV were derived at baseline, three- and six-months. Asthma did not influence HRV at baseline or following HIIT. Total power, low frequency and normalised low frequency power, and sympathovagal balance increased at three-months in HIIT, subsequently declining towards baseline at six-months. Normalised high frequency power was reduced at three-months in both groups, which was sustained at six-months. No effects of HIIT were observed in the time-domain nor in the non-linear indices. HRV was not influenced by asthma, potentially because such derangements are a function of disease progression, severity or duration. HIIT may be associated with a short-term shift towards greater sympathetic predominance during exercise, perhaps caused by physiological overload and fatigue.