Pulmonary gas exchange during high-frequency low-tidal volume ventilation (HFV) (10 Hz, 4.8 ml/kg) was compared with conventional ventilation (CV) and an identical inspired fresh gas flow in pentobarbital-anesthetized dogs. Comparing respiratory and infused inert gas exchange (Wagner et al., J. Appl. Physiol. 36: 585--599, 1974) during HFV and CV, the efficiency of oxygenation was not different, but the Bohr physiological dead space ratio was greater on HFV (61.5 +/- 2.2% vs. 50.6 +/- 1.4%). However, the elimination of the most soluble inert gas (acetone) was markedly enhanced by HFV. The increased elimination of the soluble infused inert gases during HFV compared with CV may be related to the extensive intraregional gas mixing that allows the conducting airways to serve as a capacitance for the soluble inert gases. Comparing as exchange during HFV with three different density carrier gases (He, N2, and Ar), the efficiency of elimination of Co2 or the intravenously infused inert gases was greatest with He-O2. However, the alveolar-arterial partial pressure difference for O2 on He-O2 exceeded that on N2-O2 by 5.4 Torr during HFV. The finding agrees with similar observations during CV, suggesting that this aspect of gas exchange is not substantially altered by HFV.