Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.