Asthmatic subjects with tidal expiratory flow limitation have mucociliary clearance (MC) impairment in central airways. Because tidal flow limitation develops in COPD, it is possible that regional MC in these patients also may be affected. We tested this hypothesis by measuring MC in the presence or absence of flow limitations. Patients with COPD and chronic flow limitation were compared with non-flow-limited normal volunteers. Deposition was normalized for regional lung volume and expressed as the specific central to peripheral (sC/P) ratio. In COPD subjects, clearance from the whole lung and central airways was significantly different from that of normal subjects after 20 min of observation. In the peripheral airways, there were no significant differences between COPD and normal subjects. An alternative analysis of regional MC indicated patients retained particles in central airways while normal subjects, with intact MC, emptied central airways. Thus, COPD subjects with tidal expiratory flow limitation have impaired MC in their central airways.