In summary, we have demonstrated that an abrupt reduction inFET CO 2 FETCO2 immediately precedes the onset of the central apneas in patients with ICSAS. Furthermore, we have shown for the first time that inhalation of a CO2-enriched gas or addition of dead space eliminates central apneas and hypopneas in these patients in association with an increase inFET CO 2 FETCO2 and Ptc CO 2 tcCO2 and a dampening of breath-to-breath oscillations ofFET CO 2 FETCO2 . These findings provide compelling evidence that the mechanism for initiation of central hypopneas and apneas in ICSAS is a reduction inPa CO 2 PaCO2 toward or below the apneic threshold, respectively. Our data further indicate that the mechanism for abolition of these events by CO2 inhalation and addition of dead space is by increasing and stabilizingPa CO 2 PaCO2 above the apneic threshold. Taken together, these findings indicate that ICSAS is a disorder of respiratory control system instability that isPa CO 2 PaCO2 dependent. Although the purpose of this study was not to test the clinical effects of increasingPa CO 2 PaCO2 , our findings that CO2 inhalation and addition of dead space eliminate central apneas and hypopneas point to their potential as treatments for this disorder. More studies over longer time periods will be required to test the therapeutic potential of these approaches. - www.physiology.org