Objective: Inhalation of perfluorocarbons (PFC) has been suggested as a new and promising technique of PFC delivery in animal models of severe lung injury. However, no in vitro data were available on the efficacy of PFC aerosolization during mechanical ventilation. Therefore, the aim of the in vitro study was to investigate the influence of physical properties of PFC and the ventilatory settings on the amount of PFC delivered into the lung. Design: In vitro lung model study. Setting: University research laboratory. Measurements and results: Two different PFC (PF 5080 and PFOB) were aerosolized with a PariBoy jet nebulizer. Using a PFC selective adsorber, the effect of endotracheal tube size (2 mm and 3 mm diameter) on delivery of PFC was investigated. PFC delivery was estimated by continuous measurement of weight gain of the adsorber (adsorption rate). Finally, the influence of respiratory rate and tidal volume on adsorption rate (AR) was studied. AR was significantly reduced by a decreasing tube diameter and ranged from 1.45±0.03 ml/min (no tube) to 0.93±0.03 ml/min (2.0 mm) for PF 5080 (vapor pressure 51 mmHg) and from 0.49±0.06 ml/min to 0.32±0.04 ml/min for PFOB (11 mmHg). PFC-aerosolization into a ventilatory circuit with simulation of spontaneous tidal breathing (minute volume 600 ml) reduced AR to 0.16±0.02 ml/min. During mechanical ventilation, changes in respiratory rate and tidal volume, which reduce minute ventilation, caused a decrease in AR. Conclusion: The amount of PFC that can be delivered into the lung by aerosolization is very small and is influenced by PFC properties, tube size, and ventilatory settings.