Arterial PO2 and PCO2 obtained with 2 modes of mechanical ventilation were compared in 5 premature monkeys with hyaline membrane disease (HMD) during the first 7 h of life. High-frequency oscillation (HFO) (10 Hertz) was compared with conventional positive-pressure ventilation (CMV) by matching the mean airway pressure generated by the 2 systems. Each animal served as its own control; HFO sustained an improved PaCO2 (39 +/- 8 versus 25 +/- 7 mmHg). An insignificant improvement in arterial PO2 was noted. The improved CO2 exchange occurred with a lower peak airway pressure (35 +/- 4 versus 23 +/- 11 cm H2O). Comparison of the postmortem pressure-volume curves and lung and lavage phospholipid concentrations from the animals treated with HFO in the current study to a matched set of animals treated exclusively with CMV in a previous study failed to reveal any differences. We conclude that HFO is effective in eliminating CO2 in experimental HMD without apparently altering lung biochemical or mechanical properties in a manner different from that found with CMV.