The maximal inspiratory effort recorded at the end of apnea has been considered as an index of arousal threshold in obstructive sleep apnea syndrome (OSAS). Previous investigations have shown that the arousal threshold is higher in patients with OSAS than in normal subjects. The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on the inspiratory-effort-related arousal threshold in patients with OSAS. In ten male patients, 40 episodes of apnea during stage 2 non-REM (NREM) sleep were analyzed. Apnea duration (t), esophageal pressure (Pes) at the first occluded breath (Pes1), the minimum of the three initial Pes swings (Pes min), the maximum of the three final Pes swings (Pes Max), DeltaPes (Pes Max-Pes min), RPes (rate of increase of intrathoracic pressure, DeltaPes/t), n (number of occluded breaths during apnea), DeltaPes/n, n/t, and SaO(2) were determined before and after occlusion. These apneic episodes were compared to ten episodes of apnea provoked by a mask occlusion device after 1, 7, 30, and 90 days of CPAP treatment. The therapy resulted in a decrease in the inspiratory-effort-related arousal threshold, as measured by a reduction of Pes Max, without significant changes in apnea duration and apnea-related hypoxemia. Pes1 and DeltaPes/n, which are markers of respiratory drive, significantly decreased between observations. CPAP treatment decreases the inspiratory-effort-related arousal threshold and induces a decrease in ventilatory drive in response to upper airway occlusion.