Objective: Mechanical ventilation may impair cardiovascu lar function if the transpulmonary pressure rises. Studies on the effects of high-frequency oscillatory ventilation (HFOV) on cardiovascular functions have yielded conflicting results. This study was done to compare alterations in left ventricular output and blood flow velocities in the anterior cerebral artery, internal carotid artery, and celiac artery using a Doppler ultrasound device before and 2 h after initiating HFOV in neonates with respiratory distress syndrome (RDS) or pulmonary interstitial emphysema (PIE). Design: Prospective clinical study. Setting: Neonatal intensive care unit in a perinatal center. Patients: 18 critically ill infants (postnatal age 47 +/- 12 h; mean +/- SD) were studied before and during HFOV (piston oscillator). Indications for HFOV were severe respiratory failure due to PIE (n = 10) and severe surfactant deficiency (RDS, n = 8). In the RDS group, gestational age was 27 +/- 6 weeks (range 26-31 weeks) and birthweight 1620 +/- 380 g (range 850-1970 g). In the PIE group, gestational age was 28 +/- 2 weeks (range 26-36 weeks) and birthweight 1740 +/- 470 g (range 890-2760 g). Measurements and main results: During HFOV, mean airway pressure was maintained at the same level as during intermittent mandatory ventilation in both groups (RDS, 12 +/- 2 cmH(2)O; PIE, 10 +/- 2 cmH(2)O). Compared to intermittent mandatory ventilation, several of the 12 parameters studied changed significantly (p < 0.004) during HFOV. In the RDS group, the partial pressure of oxygen in arterial blood/fractional inspired oxygen (PaO2/FIO2) ratio increased from 56 +/- 9 to 86 +/- 7 and partial pressure of carbon dioxide in arterial blood (PaCO2) decreased from 49 +/- 4 to 35 +/- 3 mmHg. In the PIE group, PaO2/FIO2 ratio increased from 63 +/- 8 to 72 +/- 7 and PaCO2 decreased from 63 +/- 7 to 40 +/- 5 mmHg. In the PIE group, heart rate decreased (135 +/- 15 be fore HFOV vs 115 +/- 14 min(-1) during HFOV) and mean systolic blood pressure increased (before 43 +/- 4 vs 51 +/- 4 mmHg during HFOV) significantly, whereas these parameters did not change in the RDS group. Left ventricular output increased significantly in the PIE group (210 +/- 34 before vs 245 +/- 36 ml/kg per min during HFOV; p < 0.004), but not in the RDS group (225 +/- 46 before vs 248 +/- 47 ml/kg per min during HFOV; k < 0.05). Shortening fraction and systemic resistance did not change in either group. In the PIE group, mean blood flow velocities in the internal carotid artery (+ 59 %), anterior cerebral artery (+ 65 %) and celiac artery (+ 45 %) increased significantly but did not change in the RDS group. Conclusions: The results show that HFOV as used in this study, improves oxygenation, CO2 elimination, and circulation in infants with RDS and PIE. However, systemic, cerebral, and intestinal circulation improved more in neonates with PIE than in those with RDS. This may be due to higher pulmonary compliance in infants with PIE when compared to those with RDS.