To determine whether initial lung volume optimization influences respiratory mechanics, which could indicate the achievement of optimal volume, we studied 17 premature infants with respiratory distress syndrome (RDS) assisted by high-frequency oscillatory ventilation. The continuous distending pressure (CDP) was increased stepwise from 6-8 cmH2O up to optimal CDP (OCDP), i.e., that allowing good oxygenation with the lowest inspired O2 fraction. Respiratory system compliance (Crs) and resistance were concomitantly measured. Mean OCDP was 16.5 +/- 1.2 cmH2O. Inspired O2 fraction could be reduced from an initial level of 0.73 +/- 0.17 to 0.33 +/- 0.07. However, Crs (0.45 +/- 0.14 ml . cmH2O-1 . kg-1 at starting CDP point) remained unchanged through lung volume optimization but appeared inversely related to OCDP. Similarly, respiratory system resistance was not affected. We conclude that there is a marked dissociation between oxygenation improvement and Crs profile during the initial phase of lung recruitment by early high-frequency oscillatory ventilation in infants with RDS. Thus optimal lung volume cannot be defined by serial Crs measurement. At the most, low initial Crs suggests that higher CDP will be needed.