Tidal volumes used in high-frequency ventilation (HFV) may be smaller than anatomic dead space, but since gas exchange does take place, physiological dead space (VD) must be smaller than tidal volume (VT). We quantified changes in VD in three dogs at constant alveolar ventilation using the Bohr equation as VT was varied from 3 to 15 ml/kg and frequency (f) from 0.2 to 8 Hz, ranges that include normal as well as HFV. We found that VD was relatively constant at tidal volumes associated with normal ventilation (7-15 ml/kg) but fell sharply as VT was reduced further to tidal volumes associated with HFV (less than 7 ml/kg). The frequency required to maintain constant alveolar ventilation increased slowly as tidal volume was decreased from 15 to 7 ml/kg but rose sharply with attendant rapid increases in minute ventilation as tidal volumes were decreased to less than 7 ml/kg. At tidal volumes less than 7 ml/kg, the data deviated substantially from the conventional alveolar ventilation equation [f(VT - VD) = constant] but fit well a model derived previously for HFV. This model predicts that gas exchange with volumes smaller than dead space should vary approximately as the product of f and VT2.