Between the lower and the upper inflection point of a quasistatic pressure-volume (PV) curve, a segment usually appears in which the PV relationship is steep and linear (i.e., compliance is high, with maximal volume change per pressure change, and is constant). Traditionally it is assumed that when positive end-expiratory pressure (PEEP) and tidal volume (V T) are titrated such that the end-inspiratory volume is positioned at this linear segment of the PV curve, compliance is constant over VT during ongoing ventilation. The validity of this assumption was addressed in this study. In 14 surfactant-deficient piglets, PEEP was increased from 3 cm H(2)O to 24 cm H(2)O, and the compliance associated with 10 consecutive volume increments up to full VT was determined with a modified multiple-occlusion method at the different PEEP levels. With PEEP at approximately the lower inflection point, compliance was minimal in most lungs and decreased markedly over VT, indicating overdistension. Compliance both increased and decreased within the same breath at intermediate PEEP levels. It is concluded that a PEEP that results in constant compliance over the full VT range is difficult to find, and cannot be derived from conventional respiratory-mechanical analyses; nor does this PEEP level coincide with maximal gas exchange.