High-frequency jet ventilation (HFJV) is one of several high-frequency techniques that are particularly valuable for treating the neonate with lung disease refractory to conventional ventilation or with pulmonary air leak. Extracorporeal membrane oxygenation (ECMO) has also emerged as a valuable rescue therapy for neonates of more than 2000 g birth weight and 34 weeks' gestation with intractable respiratory failure. With the concurrent introduction of HFJV and ECMO, the authors sought to evaluate the role of HFJV prior to the institution of ECMO therapy. The data base for 2856 neonates receiving mechanical ventilation in one unit was used to identify 73 (of 298 total) neonates treated with HFJV, who were eligible by age and weight criteria for ECMO. Patients were grouped by diagnosis, and the oxygenation index (OI) was calculated during therapy. Outcome was evaluated for mortality, and the sensitivity of the OI for predicting mortality was calculated. Neonates who survived with HFJV alone presented with an OI of 0.30 +/- 0.03 (SEM), significantly less than nonsurvivors (0.42 +/- 0.04, P = .016). Survivors responded to HFJV with a rapid decrease in OI at 1 hour (0.19 +/- 0.02, P less than .001) and 6 hours (0.15 +/- 0.01, P less than .001). Nonsurvivors did not respond significantly at 1 hour (OI = 0.33 +/- 0.04, P = not significant [NS]) or at 6 hours (OI = 0.40 +/- 0.06, P = NS). By diagnosis, neonates with respiratory distress syndrome survived more often with HFJV (28/34, 82%) than neonates with meconium aspiration (10/26, 38%) or diaphragmatic hernia (3/9, 33%). Neonates with respiratory distress syndrome seldom presented with high OI values, but the majority of those who did survived (5/7 survived with initial OI greater than or equal to 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)