ABSTRACT. We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (0, tidal volume (V,), and mean airway pressure (Fa,) produced the lowest peakto-peak alveolar pressure amplitude (Pal,) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (P,,) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. Paoz, Pacoz, P,,, and Pa,, were measured at the following settings: Fi02 = 0.5, frequency 2-28 Hz, V, 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H20. Many combinations of frequency and V, resulted in the same Pa02 and Paco2. Paw had a large effect on Pal, and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f X V : described the trends in Pa,, and blood gas tensions. As the product of f x V : increased, Paoz initially increased and then decreased, whereas Pacoz decreased and Pal,increased. No single combination of frequency, V, and Paw simultaneously provided the lowest Pal, and physiologic blood gas tensions. Adequate blood gas tensions and low Pa,, were o b t a i~d at frequencies less than 12 Hz, a V, of 2 mL/kg and a Pa, of 10 cm HzO. In healthy and lavaged rabbits Pao2 increased and Paco2 decreased as frequency increased at lower V,.Pao2 decreased as frequency increased at higher V, in lavaged rabbits only. Pa,, tended to be greater in lavaged rabbits. (Pediatr Res 27: 64-69,1990) Abbreviations f, frequency V,, tidal volume -Paw, mean airway pressure P,,, peak-to-peak tracheal pressure amplitude Selected effects off, V,, and paw on gas exchange and pressure amplitude have been studied previously in healthy and lung damaged animal models during HFOV. Oxygenation and ventilation have been shown to depend on frequency and V, (1, 2). Previous work indicating there is a relationship between C 0 2 elimination and the product of oscillatory frequency and Vt [VC02 = a(Qb(V,)" where a, b, c are constants] (3, 4) led us to evaluate the relationship of arterial blood gas tensions to the product f x V? (5). We observed that many combinations of frequency and V, produced equivalent blood gas tensions and that the composite variable f x V : was a good descriptor of our mean arterial blood gas tensions during HFOV in healthy rabbits. Others have found that different combinations of frequency, V, and Paw can produce equivalent blood gas tensions (3, 4) but the resultant pressure swings in the trachea and alveolus may not be equivalent. Near the resonant frequency of the respiratory system, pressure swings in the alveolus may exceed those at the airway opening during HFOV (8, 9). Allen et al. (10) reported that the ratio, Pa,,/P,,, increased as &, increased near the resonant frequency in excised rabbit lungs. Although increasing Paw has not been shown to improve gas exchange in healthy animals (1 1) it does improve oxygenat...