To investigate the difference in ventilatory response to exercise between children and young adults, we administered a treadmill progressive exercise test to seven boys (aged 8 to 11 y [group A]) and six male young adults (aged 14 to 21 y [group B]), who had a history of Kawasaki disease without significant coronary arterial lesions, and analyzed their arterial blood gases. There was no significant difference in arterial PO2 or the end-tidal to arterial oxygen tension difference during exercise between groups A and B. The arterial PCO2 (PaCO2) at the ventilatory anaerobic threshold and at peak exercise was significantly lower in group A than in group B (p < 0.05). The arterial to end-tidal carbon dioxide tension difference at peak exercise was significantly greater in group B than in group A (p < 0.05), whereas there was no significant difference at rest or at the ventilatory anaerobic threshold level. The arterial to end-tidal carbon dioxide tension difference at peak exercise was correlated with tidal volume (p < 0.01) and carbon dioxide production (p < 0.05) at peak exercise in all subjects. Although improvement in the physiologic dead space/tidal volume ratio during exercise was smaller in group A than in group B, there was no significant difference in total alveolar ventilation during exercise. However, the total carbon dioxide production during exercise was significantly smaller in group A than in group B. These data suggest that PaCO2 during exercise is better estimated by end-tidal carbon dioxide tension in children than in young adults, that there is a significant difference in change of the PaCO2 during exercise between children and young adults, and that the decrease in PaCO2 in children is related to the mismatch between well-maintained alveolar ventilation and immature metabolic development in the working muscles during moderate-to-severe exercise.