Corticosteroids and surfactant operate by clearly different mechanisms. The steroids stimulate (via the fibroblast-pneumonocyte factor) production of surfactant phospholipids by alveolar type II cells, enhance the expression of surfactant-associated proteins, reduce microvascular permeability, and accelerate overall structural maturation of the lungs. However, the increment in pool size of surfactant resulting from antenatal treatment with corticosteroids is trivial relative to the dose of exogenous surfactant required for successful prophylaxis at birth. Data from animal experiments indicate that antenatal corticosteroids and postnatal surfactant treatment have synergistic beneficial effects on neonatal lung function, and that these effects can be further potentiated by adding antenatal administration of thyrotrophin releasing hormone (TRH). Promising results have been obtained in recent clinical trials combining antenatal treatment with corticosteroids and TRH for prevention of RDS.