The aim of this study was to examine whether preserved spontaneous breathing (SB) supported by proportional-assist ventilation (PAV) would improve cardiac output (CO) during partial liquid ventilation (PLV) in rabbits with and without lung disease if compared with time-cycled, volume-controlled ventilation (CV) combined with muscle paralysis (MP). PLV was initiated in 17 healthy rabbits and 17 surfactant-depleted rabbits using 12 to 15 ml/kg of perfluorodecaline. Both ventilatory modes, SB+PAV and CV+MP, were applied in random sequence using a crossover design. CO was measured by thermodilution. CO was significantly higher during SB+PAV than during CV+MP: 136 +/- 21 ml/kg x min (mean +/- SD) versus 120 +/- 30 ml/kg x min (p = 0.004) in healthy rabbits, and 147 +/- 19 ml/kg x min versus 111 +/- 13 ml/kg x min (p < 0.0001) in surfactant-depleted rabbits, resulting in an improved oxygen delivery. This difference was mainly caused by a larger stroke volume during SB+PAV, whereas there was little change in heart rate. In surfactant-depleted rabbits, SB+PAV resulted in improved arterial blood pressure and arterial and mixed venous pH and in a higher PaO2 at the same level of PEEP and mean airway pressure. We conclude that during PLV, CO is higher during SB+PAV than during CV+MP, resulting in an improved oxygen delivery. In surfactant-depleted rabbits, improved CO, oxygen delivery, and arterial blood pressure resulted in higher pH, possibly reflecting improved tissue perfusion and oxygenation.