Although there has been extensive research into the control of breathing in adults with chronic obstructive lung diseases, there is little information in this area in children with cystic fibrosis (CF). The purpose of this study was to investigate the respiratory response of children with CF to CO2 under hyperoxic conditions. Using a standard CO2 rebreathing technique, we studied 14 children with CF. We evaluated their response to CO2 in terms of ventilation (VE), mean inspiratory flow rate (VT/TI), and the pressure generated at the mouth after 0.1 s of an inspiratory effort against an occlusion (P0.1). In order to understand the contributions of the rib cage and abdominal components to ventilation, we assessed the volume change in each compartment by attaching magnetometers to the chest and abdomen. Overall changes in lung volume were assessed in a volume displacement plethysmograph. We found that, when corrected for the height of the child, the slope of VE versus end tidal CO2 (PETCO2), as well as the slope of VT/TI versus PETCO2 correlated significantly with the degree of airway obstruction as expressed by the forced expiratory flow between 25 and 75% of vital capacity. The values for P0.1 were all within the normal range and showed no correlation with the degree of airway obstruction. The contribution of the rib cage and abdomen to ventilation during rebreathing was similar to that previously reported for adults. No changes were observed in functional residual capacity during rebreathing. We showed that tests involving a mechanical response to CO2 correlated with the degree of airway obstruction, but there was no evidence that the neuromuscular drive was abnormal.