Elimination of CO2 during liquid ventilation is dependent on flow, diffusion, and the liquid's capacitance for CO2. Maximum expiratory flow (Vmax) and diffusion dead space were measured in vivo in 12 young cats during liquid fluorocarbon (FC-80) ventilation to determine the effect of breathing frequency on maximum CO2 elimination. All animals were maintained (PaO2 = 255 +/- 19 SEM mm Hg, PaCO2 = 35 +/- 1 SEM mm Hg, pH = 7.31 +/- 0.01 SEM) within physiologic range during 1-4 h of liquid ventilation. The Vmax in air (26 +/- 1 SEM liter/min) and in liquid (1.2 +/- 0.2 SEM liter/min) was determined by volume displacement plethysmography. Diffusion dead space (VDdiff) during liquid ventilation as a ratio of alveolar volume (VA) was well correlated (r = 0.84, p less than 0.005) with the average time (tav) the liquid was in the lung [VDdiff/VA = 0.89 e (-0.053 tav)]. Alveolar ventilation, CO2 elimination (VCO2), and PaCO2 were not affected by breathing frequency (f) when tidal volume was adjusted appropriately during steady state liquid ventilation. Predicted maximum CO2 elimination (VCO2max) determined from Vmax and VDdiff was 24 ml/min at a f of 3-3.5 breaths/min. The maximum was found to be strongly dependent on f with much less dependency on fixed dead space (anatomic plus equipment) and wave shape characteristics. Elimination of CO2 decreased at low values of f due to inadequate ventilation and at high values of f due to inadequate diffusion time. From a comparison of experimentally determined steady state VCO2 to theoretically predicted VCO2max, the results demonstrate a f-related functional reserve capacity for CO2 elimination during liquid ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)