We investigated the quasi-static pressure-volume (P-V) hysteresis of the normal canine lung in vivo by performing 15-s flow interruptions at various points throughout the breathing cycle in mechanically ventilated anesthetized paralyzed dogs. By measuring the transpulmonary pressure (Ptp) at 5 s after each interruption, we built up a quasi-static P-V loop of the lungs. We found, however, that the area of the loop was significantly smaller (by a factor of 4-6) than has been reported by others for the isolated canine lung. We also found the hysteresis loop area of the chest wall to be of similar magnitude. If we measured Ptp 10-15 s after interruption, we found it always decreased at a rate expected to result from continuing gas exchange in the lungs. We conclude that 1) the areas of the quasi-static P-V loop in vivo for the total respiratory system, as well as the lungs and chest wall separately, are significantly smaller than has been reported previously for isolated lungs and 2) continuing gas exchange in the lungs places a lower limit on the frequencies (equivalent to flow interruptions of greater than 5- to 7-s duration) at which the P-flow-V behavior of the lungs in vivo can be considered in purely mechanical terms.