Liquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (Qt) in several animal species, casting doubt as to its feasibility. This study tested whether Qt could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous Qt measurement, and subjected to 2 hr of liquid breathing. PaCO2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and PaO2 greater than 80 torr (greater than 10.7 kPa). Additional colloid was given during liquid breathing if Qt decreased to less than 90% of preliquid breathing values. Four piglets maintained Qt throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for Qt 82% to 89% of the baseline value, after which Qt rapidly increased to greater than 90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing. Qt is readily maintained during liquid breathing in properly hydrated animals.