The objective of this study was to quantitate perfluorochemical (PFC) elimination kinetics during partial liquid ventilation (PLV) following an initial fill with or without hourly dosing. Young New Zealand rabbits were studied in two groups: Gr I (n = 6), PLV with a single dose of PFC liquid (perflubron: LiquiVent, Alliance Pharmaceutical Corp.); and Gr II (n = 5), PLV with PFC liquid and multiple hourly dosing . All rabbits were studied for 4 h, following initial instillation of a volume of PFC liquid equal to the measured gas functional residual capacity. Animals were ventilated at a constant breathing frequency (30 br/min), tidal volume (9.3+/-0.3 SE mL/kg), positive end expiratory pressure (4 cm H2O), and inspiratory time (0.30 s). PFC saturation of mixed expired gas (PFC-Sat) was assessed with a thermal conductivity analyzer, and PFC elimination was calculated from PFC-Sat, minute ventilation, and temperature of the expired gas. In GR II, PFC was supplemented hourly at a volume determined by PFC elimination calculations. The results demonstrated a decrease in PFC-sat and PFC loss with time, independent of group (P< 0.05). In addition, with hourly supplementation (GR II), PFC-Sat and PFC elimination over time was significantly (P < 0.05) greater than in animals (GR I) which did not receive additional doses. These data demonstrate that the PFC elimination rate is not constant and is related to the amount of PFC in the respiratory system. This may have occurred due to distributional differences of ventilation and PFC liquid between the single and multiple dosing groups. These findings also suggest that evaluation of PFC concentrations in expired gas may be a clinically useful index of intrapulmonary PFC distribution during PLV, and that maintained elevation of expired gas PFC saturation may guide optimal PFC dosing intervals and distribution to maximize protection against barotrauma.