To investigate the role of high frequency oscillation (HFO) in promoting meconium clearance from the airway, we used a commercially available ventilator configured with maximal expiratory flow exceeding inspiratory flow (asymmetric HFO or AHFO). We hypothesized that AHFO would move meconium in an expiratory direction (toward the ventilator). We first tested our hypothesis in vitro and, later, in vivo using the neonatal piglet. In vitro experiments using a Plexiglas airway confirmed meconium movement in an expiratory direction when bias ratio was > or = 2. For in vivo experiments, each piglet received a 3 mL/kg intratracheal bolus of a 44 g/100 mL meconium mixture followed by 45 min of mechanical ventilation. Then, in part 1, the piglet was placed in a 15 degree head down tilt position and randomized to either AHFO [ratio of inspiratory time/expiratory time (I:E) of 70:30] or HFO (I:E ratio of 30:70). After 30 min of either AHFO or HFO, the piglet was crossed over to the alternate strategy for an additional 30 min. For part 2, we maintained the piglet on either AHFO or HFO continuously for 4 h. Results demonstrate that, although there was a tendency for larger volumes of meconium to be aspirated from the airway during AHFO in part 1 experiments, there was no difference found in part 2. We also found no significant differences in blood gases or hemodynamic measurements between AHFO and HFO during the prolonged observation period in part 2 of our study. We conclude that AHFO is of no benefit in the treatment of meconium aspiration syndrome.