As previous studies have demonstrated a neuromechanical inhibition of inspiratory motor output during normocapnic passive mechanical ventilation in awake22 and sleeping subjects,11,23 the inhibition threshold could depend not only on the carbon dioxide level but also on mechanical influences. In this study, we did not add carbon dioxide to the admission filter of the ventilator to test its direct influence on the inhibition threshold for a similar effective ventilation and a similar level of hypoxia. Indeed, in order to test the respective influences of neuromechanical inhibition and of chemical inhibition, one should test the subjects at a given mechanical condition and different carbon dioxide levels. However, at increasing carbon dioxide levels, it is not possible to maintain a fixed neuromechanical coupling during nIPPV, even if the parameters of the ventilator are left unchanged. In such situation, we have previously shown that the actual Vt volume and effective V̇e will change due to glottic widening despite fixed Vtd and V̇ed.,2–3 Therefore, this type of experiment would not allow separation of neuromechanical from chemical inhibition when using noninvasive ventilation. It seems obvious that in order to lower Petco2, one has to increase effective ventilation, so that lower chemical stimuli (carbon dioxide) will be associated with higher mechanical stimuli (effective ventilation), both of which could inhibit the VRH. Although this was true in our study for subjects 1, 2, and 4, subject 3 showed a different pattern: on N2 run 11, the effective ventilation was 7.42 L/min, the Petco2 was 29.2 mm Hg, and no VRH was recorded. On N2 run 32, the effective ventilation was much higher (13.55 L/min) for a similar level of Petco2 (29.3 mm Hg), and a VRH was elicited (Table 2). Thus, we had a response despite a higher level of mechanical inhibition for a similar chemical stimuli. However, this is not a sufficient proof that the mechanical inhibition can be ruled out as associated with the chemical inhibition, since the subject was not in the same state of vigilance on the two occasions. Another way of tackling this problem is to consider whether the VRH can be abolished not only by a carbon dioxide threshold but by a V̇e threshold. We were not able to find for effective V̇e a clear-cut threshold below where no VRH could be elicited as we did for Petco2. This suggests, without proving it, that the VRH seems to be mainly determined by chemical rather than by mechanical influences.