The role of high-frequency jet ventilation (HFJV)/continuous positive airway pressure (CPAP) and HFJV/intermittent mandatory ventilation (IMV) in the treatment of surgical patients with the adult respiratory distress syndrome were evaluated. To compare the efficacy of HFJV to IMV at a constant FiO2 and positive end-expiratory pressure, patients in surgical intensive care were randomized to receive IMV/CPAP therapy or one of three modes of HFJV: (1) HFJV/CPAP alone, (2) HFJV/CPAP + IMV (1), or (3) HFJV/CPAP + IMV (2). Each patient served as his own control. During comparison of HFJV/CPAP + IMV (1) to HFJV/CPAP + IMV (2) (n = 9) and HFJV/CPAP to HFJV/CPAP + IMV (1) (n = 7), cardiac output, PaCO2, PaO2, PvO2, and variables consisting of intrapulmonary shunt fraction (Qsp/Qt), PaO2/FiO2 ratio, and A-a gradient were calculated. The subgroup placed on HFJV/CPAP demonstrated a fall in PaO2 of 13 torr (p = NS; n = 5). HFJV/CPAP + IMV (1) compared with HFJV/CPAP significantly (p less than 0.005) increased PaO2 by 52 +/- 24 torr and decreased Qsp/Qt by 8.9 +/- 1.0 (p less than 0.025). Cardiac output remained unchanged. Comparison of HFJV/CPAP + IMV (2) to HFJV/CPAP + IMV (1) demonstrated a significant improvement in oxygenation (p less than 0.025), but of lesser magnitude (8.4 +/- 11 torr). PaO2/FiO2 ratio and A-a gradient improved in both IMV (1) and IMV (2) subgroups. Oxygenation and ventilation/perfusion (V/Q) matching significantly improved with HFJV/CPAP + IMV (1), to a greater magnitude than with HFJV/CPAP + IMV (2) or HFJV/CPAP alone, and was the preferred method of ventilatory support.