Despite advances in neonatology, some infants do not respond to current pharmacologic and ventilatory techniques. Others suffer chronic lung disease, require prolonged ventilatory support, and experience significant morbidity during infancy due to the elevated inflation pressures used to treat their respiratory problems. Over the past 30 years, results of studies in premature animals as well as clinical trials have demonstrated that ventilation with oxygenated perfluorochemical (PFC) fluids provides effective gas exchange and improved lung mechanics. PFC fluids are biologically inert, have a high gas solubility and a low surface tension, and are nonbiotransformable. With liquid ventilation, alveolar pressures are low because the high surface tension of the gas-lung interface in eliminated. Potential neonatal applications include surfactant deficiency, persistent pulmonary hypertension, meconium aspiration, diaphragmatic hernia, pneumonia, and a vehicle for drug delivery. In order to develop a nursing care plan for the liquid-ventilated infant, nurses need knowledge of the physiologic changes involved in liquid ventilation, as well as its mechanics.