Objective: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV), This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. Design: Randomized trial. Setting: University animal research facility. Subjects: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- SD). Interventions: After pulmonary lavage (target pan, < 100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an FIO2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV, PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao(2), Paco(2), tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. Main Results: pan, and compliance were significantly higher in PLV rabbits compared with controls (P < .05, analysis of variance for repeated measures). All other parameters were similar in both groups. Conclusions: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.