Flow limitation during sleep occurs when the rise in esophageal pressure is not accompanied by a flow increase which results in a non-rounded inspiratory flow shape. Short periods of flow limitation ending in an arousal or in a fall in SaO2 (hypopnea or upper airway resistance syndrome) are detrimental but the role of prolonged periods of flow limitation (PPFL) has not yet been clarified. This is important not only for diagnosis but also for nasal continuous positive airway pressure (CPAP) titration, especially for the automatic devices that need to be setup. The aim of this study was to analyze the effects of PPFL. We compared the behavior of the mean end-expiratory systemic blood pressure (SBP), end-tidal CO2, esophageal pressure and the pattern of breathing during a period of normal breathing at optimal (CPAP) and during PPFL at suboptimal CPAP in 14 patients with sleep apnea/hypopnea syndrome during a full polysomnography CPAP titration. The mean values of the parameters studied, at optimal and suboptimal CPAP were (1) SBP 92+/-13 vs. 91+/-15 mmHg (P: ns). At suboptimal CPAP, swings of blood pressure were associated with changes in pleural pressure; (2) SaO2 97.5+/-1.2 vs. 96.5+/-1.6 (P: 0.03), (3) end-tidal CO2 43.5+/-4 vs. 49.5+/-4 (P:0.001); (4) oesophageal pressure, 10.5+/-4 vs. 37.6+/-15 cmH2O (P:0.001) and (5) pattern of breathing: minute ventilation 6.6+/-1.4 vs. 6.1+/-1.2L/min (P: ns) and inspiratory time 1.24+/-0.3 vs. 1.66+/-0.4s (P:0.001). It can be concluded that PPFL induces significant physiological changes. Nevertheless, given the scant literature, clinical studies are warranted to elucidate the clinical role of these physiological changes.