ABSTRACT. We studied the hemodynamic consequences during the first 24 h of life in premature baboons (140 d) with hyaline membrane disease that were treated with high-frequency oscillatory ventilation (HFOV) or conventional intermittent mandatory ventilation (IMV). Cardiac output and organ blood flow were measured at three timepoints using the radiolabeled microsphere technique. Seven of seven HFOV and six of eight IMV animals survived_the 24-h period. By design, initial mean airway pressus (P,,) was higher in the HFOV group (p < 0.01). HFOV Pa, was progressively reduced during the study period because of improving oxygenation as measured by the arterial to alveolar oxygen ratio. In contrast, it was necessary to increase Paw in the IMV animals to maintain the arterial to alveolar oxygen ratio. By 23 h, the IMV group required higher Pa, than the HFOV group (p < 0.05) and had a lower arterial to alveolar oxygen ratio (p < 0.05). We found no significant differences in left ventricular output, effective systemic flow, organ blood flow, or central venous pressure between the two groups at 3, 8, or 23 h. The HFOV strategy used in our study resulted in significant improvement in oxygenation during the initial 24 h of treatment without adverse effect on left ventricular output, cerebral blood flow, or central venousjressure. We conclude that when appropriate changes in Pa, are made during HFOV in response to improvement in arterial oxgenation and changes in lung inflation as assessed by chest radiographs HFOV can be achieved without depressing cardiovascular dynamics more than during conventional therapy with IMV. (Pediatr Res 29: 160-166,1991) Abbreviations CVP, central venous pressure Fi02, fraction of inspired oxygen HFOV, high-frequency oscillatory ventilation HMD, hyaline membrane disease IMV, intermittent mandatory ventilation LVO, left ventricular output -Paw, mean airway pressure PEEP, positive end expiratory pressure PIP, peak inspiratory pressure