Dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi) are observed in patients with chronic obstructive pulmonary disease (COPD) and flow limitation. Several reports suggest that PEEP levels approaching PEEPi reduce inspiratory load due to PEEPi, without further hyperinflation. Hence PEEP should not increase intrathoracic pressure or affect hemodynamics and gas exchange. To verify this hypothesis, the effects of PEEP (0 to 15 cm H2O) on respiratory mechanics, hemodynamics, and gas exchange were studied in nine COPD patients during controlled mechanical ventilation. PEEP levels approaching PEEPi (9.8 +/- 0.5 cm H2O) did not affect the expiratory flow/volume relationship, confirming the presence of flow limitation. PEEP levels of 5 and 10 cm H2O did not change lung volume and PEEPi in the respiratory system (PEEPtot,rs) and chest wall (PEEPtot,cw) or affect hemodynamics and gas exchange. When applied PEEP overcame PEEPi, changes in lung volume and the expiratory flow/volume relationship were observed. PEEPtot,rs and PEEPtot,cw also increased. Under these circumstances, PEEP increased static elastance in both the respiratory system and the chest wall, reducing cardiac index and affecting hemodynamics and gas exchange. Our data show that in mechanically ventilated COPD patients with PEEPi due to flow limitation, PEEP levels exceeding the 85% of PEEPi (Pcrit) caused further hyperinflation and compromised hemodynamics and gas exchange.