Animal experiments and clinical trials have shown that the neonatal respiratory distress syndrome (RDS) can be treated effectively by surfactant replacement via the airways. This treatment facilitates the resorption of fetal pulmonary fluid, promotes uniform air expansion of the lungs, enhances gas exchange, reduces the protein leak across the alveolar epithelium, and prevents the development of bronchiolar epithelial lesions during artificial ventilation. Data from recent animal experiments indicate that surfactant replacement prevents epithelial lung lesions also during high frequency ventilation. Surfactant replacement restores blood gases to normal in adult experimental animals with severe respiratory insufficiency induced by repeated lung lavage, suggesting that this type of treatment might be effective in clinical adult RDS.