This paper presents the rationale for surfactant replacement therapy. In 6 animal models in which respiratory failure was induced by damaging the bronchial surfactant, surfactant depletion by lung lavage, by free oxygen radicals, by influenza virus and by anti-lung serum, it is demonstrated that surfactant instillation always led to an improvement in gas exchange and lung mechanics. A first clinical trials shows that surfactant instillation also improved lung function in a patient with severe respiratory failure. It is speculated that surfactant replacement therapy will become an acceptable therapeutic measure for treating lung failure in patients suffering with ARDS.