The aim of this study was to evaluate the efficacy of physiological rate-responsive pacemakers (Closed Loop Stimulation--CLS) to pace pediatric and late adolescent patients undergoing rest, mental, standing, and exercise testing. Dual-chamber pacemaker is increasingly indicated for young patients. A new physiological pacing mode based on the indirect measure of ventricular contractility (CLS), has shown interesting results in adults, while no data on pediatric patients are available. RR intervals and beat-to-beat systolic and diastolic pressures were monitored in 12 pediatric patients (6 males, mean age 17 years [12-22 years]) who had a transvenous implant of Inos2+-CLS dual-chamber pacemaker (Biotronik GmbH, Berlin, Germany) and endocardial leads. All the patients showed correct electrical parameters at the implant and during the follow-ups. Paced RR intervals decreased significantly (F = 7.28, P = 0.01) from 0.85 +/- 0.08 seconds (rest) to 0.73 +/- 0.10 seconds (mental) and to 0.75 +/- 0.010 seconds (standing); systolic/diastolic pressure was significantly higher (F = 12.2, P = 0.002/F = 13.6, P = 0.001) in mental (134.4 +/- 19.9/74.4 +/- 8.1 mmHg) with respect to rest (115.1 +/- 18.3/61.0 +/- 6.1 mmHg), and standing (118.7 +/- 23.9/67.3 +/- 0.1 mmHg). During exercise the paced RR interval showed significant decrease of about 35% from baseline to maximum load (F = 24.90, P = 0.001) and systolic pressure increased significantly (F = 4.91, P = 0.019) by about 34% from baseline to maximum load. The comparison between paced and spontaneous rates showed very similar values and trend. In addition, CLS mode does not seem to overrun the spontaneous heart activity, when present. This is a study to evaluate CLS pacing in pediatric and late adolescent patients. The study shows that CLS pacing responds to both physical and non-physical stressors, providing physiological pacing rates, as previously observed in adults.