The present study evaluated whether high-frequency oscillations (HFO) with biased flow profiles applied at the airway opening are capable of altering mucus clearance. In eight anesthetized sheep, artificial mucus (100 P) was infused continuously (1 ml/min) into the left main bronchus via a cannula inserted through the dorsal wall of the left main bronchus after thoracotomy. Outcoming mucus was collected every 10 min from the end of a cuffed orotracheal tube. Animals were ventilated with a Harvard respirator at a low frequency with superimposed HFO at 14 Hz with asymmetrical waveforms generated by a digitally controlled electromagnetic piston pump (expiratory bias: peak expiratory flow 3.8 l/s, peak inspiratory flow 1.3 l/s; inspiratory bias: reverse of expiratory bias). The influence of posture and of HFO airflow bias on mucus clearance was determined. In the horizontal position, mucus clearance with expiratory biased HFO was 3.5 +/- 2 (SD) ml/10 min. Head-down tilt produced a clearance of 3.1 +/- 3 ml/10 min; addition of HFO with expiratory bias increased clearance to 11.0 +/- 2.0 ml/10 min (P less than 0.05). No clearance occurred with inspiratory biased HFO during head-down tilt. These results indicate that expiratory biased HFO at the airway opening can clear excessive airway secretions and augment clearance by postural drainage.