There is a severe defect in the surfactant system in adult respiratory distress syndrome (ARDS). According to animal studies oxidant injury acutely alters the synthesis and secretion of surfactant. Plasma-derived surfactant inhibitors cause an early decrease in surface activity in high permeability lung oedema. Alveolar inflammation severely disturbs the surfactant system as a result of enzymatic breakdown of its components and inhibition of surfactant function. Analysis of bronchoalveolar lavage fluid obtained following unilateral irradiation of the lung revealed a striking increase in inhibitory serum proteins and a decrease in surfactant components (SP 35 apoprotein, phosphatidylglycerol, saturated phosphatidylcholine), before appearance of irradiation pneumonitis. In lysinuric protein intolerance (LPI), an autosomal recessive disorder in renal-intestinal-hepatic diamino acid transport, there is an increased risk of ARDS. In asymptomatic LPI the concentration of diamino acids in alveolar epithelial lining was strikingly increased, suggesting that the basolateral epithelial transport defect additionally involves alveolar epithelium and predisposes to ARDS.