Intrinsic positive end-expiratory pressure (PEEPi) is routinely determined under static conditions by occluding the airway at end-expiration (PEEPi,st). This procedure may be difficult in patients with chronic obstructive pulmonary disease (COPD) during spontaneous breathing, as both expiratory muscle activity and increased respiratory frequency often occur. To overcome these problems, we tested the hypothesis that the difference between maximum airway opening (MIP) and maximum esophageal (Ppl max) pressures, obtained with a Mueller maneuver from the end-expiratory lung volume (EELV), can accurately measure PEEPi,st. Using this method, we found that, in eight ventilator-dependent tracheostomized COPD patients (age 71+/-7 yr), PEEPi,st averaged 13.0+/-2.9 cm H2O. That measurement was validated by comparison with a reference static PEEPi (PEEPi,st-Ref) taken at the same EELV adopted by patients during spontaneous breathing, and measured on the passive quasi-static pressure-volume (P/V) curve of the respiratory system, obtained during mechanical ventilation. PEEPi,st-Ref averaged 13.1+/-3.0 cm H2O, i.e., a value essentially equal to PEEPi,st measured by means of our technique. We conclude that PEEPi,st can be accurately assessed in spontaneous breathing COPD patients by the difference between MIP and Ppl max during the Mueller maneuver.