To evaluate the predictive values of oxygenation index (OI), arterial-alveolar oxygen tension ratio (a/APO)₂, and alveolar-arterial oxygen gradient ((A-a)DO₂) for early recognition of responsiveness to high frequency oscillatory ventilation (HFOV) in very low birth weight infants with respiratory distress syndrome (RDS), 23 infants who received HFOV treatment for severe RDS after failing to be improved with conventional mechanical ventilation from July 1995 to February 1998 were included. Twelve infants survived with HFOV (Responder group), while 11 infants could not maintain oxygenation with HFOV and died (Non-responder group). Clinical record (of each patient) were retrospectively reviewed and compared with the respiratory indices. Mean (A-a)DO₂ was significantly lower in the responder group than in the non-responder group at 2 hr after HFOV (p=0.024), and the difference was more remarkable at 6 hr(p=0.005). Death in the patient with (A-a)DO₂ over 350 at 2 hr after HFOV therapy was 100% in sensitivity and 80% in specificity. The earliest significant difference of mean a/APO2 between two groups was noted at 6 hr after HFOV treatment (p=0.019). OI showed no significant differences between two groups. In summary, (A-a)DO₂ was the most effective and sensitive respiratory index for predicting the responsiveness to HFOV in infants with severe RDS providing due as early as 2 hr.