We studied the sequential pattern of lung filing by measuring the slope of the alveolar plateau in single breath helium washouts after inhaling a bolus at a lung volume (VI) equivalent to 20. 40, 60 and 80% of vital capacity (VC). In seated subjects, prone dogs, both with the chest intact and wide open, and individual canine lobes, slopes at VI = 20% VC were more positive than those at VI = 80% VC, indicating a "first in - last out' pattern. Furthermore the range of slopes, which reflects the magnitude of sequencing, was comparable in the four situations. We conclude that sequential filing and emptying of the lung has predominantly an intraregional basis. A two compartment optimization analysis using single exponential pressure-volume curves suggests that only a small proportion of the lung needs to behave differently to produce the sequencing observed in individual lobes.