High frequency jet ventilation (HFJV) was used to treat 176 infants who were either failing to respond to conventional mechanical ventilation (CMV) or demonstrating pulmonary air leak. The median birthweight for infants treated with HFJV was 1530 g, median gestational age was 31 weeks. Median duration of therapy with HFJV was 3.0, with a range of 0.1 to 27 days. During the first 24 hours of treatment, mean airway pressure decreased from 16.2 +/- 0.3 (Mean +/- SEM) cmH2O to 12.2 +/- 0.3 cmH2O, while mean PaO2 increased from 65.3 +/- 3.0 torr to 93.3 +/- 3.0 torr during the same time period. Simultaneously, mean PaCO2 decreased from 46.4 +/- 1.5 torr to 36.6 +/- 1.0 torr, although peak inflating pressure decreased from 34.3 +/- 0.7 cmH2O to 30.1 +/- 0.8 cmH2O. Ninety-five (54%) infants treated with HFJV survived. Of 123 infants with RDS 75 (61%) survived. The rate of complications for HFJV patients was similar to that seen with CMV in our nursery. This study suggests that HFJV provides improved oxygenation and ventilation of infants at lower mean and peak pressures compared to conventional mechanical ventilation. HFJV combined with CMV may be a valuable adjunct to therapy in infants with severe lung disease.