The vasoactive products of uncontrolled protease activity can play an important role in the pathogenesis of respiratory distress syndrome in newborn infants. In this study alpha-2-macroglobulin, which has antiproteolytic activity, was studied in the first few hours of life in preterm infants with and without respiratory distress syndrome. Mean plasma alpha-2-macroglobulin levels were found to be similar in both groups. These findings implicated that alpha-2-macroglobulin has no significant role in the pathogenesis of respiratory distress syndrome.