The benefits of mechanical ventilation with positive end-expiratory pressure (PEEP) are well documented, especially for patients with acute respiratory failure. PEEP increases functional residual capacity (FRC) and reduces closing volume (CV) and ventilation-perfusion mismatching. Little is known about the effects of PEEP in patients with chronic obstructive pulmonary disease, where closing volume and ventilation-perfusion mismatching are increased. We investigated the effects of PEEP in a canine model of panlobular emphysema (PLE). METHODS. After completion of control-period measurements, PLE was induced in eight dogs by intratracheal application of 20 ml aerosolized 16% papain solution. Three weeks later the effects of continuous positive-pressure ventilation (CPPV, PEEP 10 cmH2O) on gas exchange, FRC, and CV were investigated. Conventional intermittent positive-pressure ventilation (IPPV) served as reference. Measurements of CV were done using both the foreign gas bolus method and the single-breath oxygen test. FRC was determined by the nitrogen dilution technique. RESULTS. The papain-induced emphysema produced a deteriation in oxygenation, enlargement of FRC and CV, and an increase in quasi-static lung compliance. CPPV led to a further increase of FRC, but gas exchange was not improved nor was CV reduced. In the PLE period, mean pulmonary arterial pressures (MPAP) were higher during both modes of ventilation. CPPV tended to increase MPAP and pulmonary capillary wedge pressure when compared with IPPV. Systemic hemodynamic conditions were stable throughout the experiment. CONCLUSIONS. The application of PEEP to emphysematous lungs seemed to enlarge FRC, predominantly in the nondependent rather than in the dependent lung regions, which are prone to airway closure. In patients with emphysema, ventilation with PEEP may further deteriorate the impaired distribution of ventilation and thus counteract any improvement of gas exchange.