The use of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) has been advocated by some to assist in the weaning process of patients receiving mechanical ventilation for respiratory failure. The efficacy of this technique and its effect on respiratory system mechanics are not well understood. The theoretical advantage of CPAP or PEEP during the weaning process can be obliterated if excessive dynamic hyperinflation is induced. A key determinant of the individual response to this proposed weaning technique is the recognition of the presence or absence of expiratory flow limitation. We studied the effect of progressively increased levels of applied PEEP on isovolume expiratory flow and end-expiratory lung volume in seven patients during controlled mechanical ventilation. In the absence of expiratory flow limitation, passive expiratory flow decreased and end-expiratory lung volume increased when any level of PEEP was applied. In contrast, flow-limited patients did not demonstrate a change in isovolume expiratory flow or end-expiratory lung volume until the applied PEEP reduced the driving pressure for expiratory flow below a critical value. All patients demonstrated dynamic hyperinflation during controlled ventilation as evident by the existence of intrinsic PEEP. The nominal value of applied PEEP that caused a reduction in isovolume expiratory flow was unrelated to the initial level of intrinsic PEEP. The clinical implications of these findings with respect to CPAP therapy during weaning from mechanical ventilation are discussed.