Ethane washout during low tidal volume (25-100 ml) high-frequency (3-40 Hz) ventilation (HFV) was studied in seven excised dog lungs. The lungs were initially equilibrated with 1% ethane, and then the concentration of ethane was monitored by mass spectrometry from multiple anatomic sites along the tracheobronchial tree during washout. We observed that the lung changed from a uniform distribution of ethane concentrations to a nonuniform distribution by a three-phase process. The first phase was nearly complete within the first 15 s and probably corresponds to concentration gradients being established in the central airways. During the second phase of washout, which lasted for several minutes, the concentrations in the various alveolar regions diverged. In the final phase, the regional concentrations remained at fixed ratios, and washout from all sites in the lung was at a constant fractional rate. These data are consistent with a model in which the duration of the second phase and the magnitude of the regional concentration differences established in this phase are dependent on both the magnitude of differences between regional transport paths and the nature of regional coupling by a common transport path to the airway opening.