Effective gas exchange can be achieved in normal dogs by ventilation at frequencies of 4-20 Hz using stroke volumes (SV) smaller than the anatomic dead space. CO2 elimination is largely a function of tracheal SV-frequency product (Vosc) in anesthetized, paralyzed dogs with normal lungs. To determine the effect of constriction of small airways on gas exchange during such high-frequency ventilation (HFV), we ventilated five anesthetized, paralyzed, and vagotomized dogs via a tracheal cannula before and during intravenous histamine infusion. Vosc was varied by varying the frequency while keeping SV constant. For low Vosc, CO2 elimination (VCO2) increased directly with Vosc during control and histamine experiments. At high Vosc, VCO2 continued to increase directly with Vosc during the control study, but during histamine infusion VCO2 was lower than control values. Eucapnia could be maintained in each dog during HFV, even during airway constriction. During histamine infusion the frequency-dependent mechanical properties of the lung influence the delivery of the HFV SV to the respiratory zone, and this may explain the lower VCO2 observed.