In the serum of normal prematures and premature infants with respiratory distress syndrome, plasminogen was absent. In mature newborns plasminogen levels were low, as compared to adults. In the euglobulin fraction of plasma, plasminogen level was highest in mature newborns, lower in healthy prematures, and lowest in prematures with respiratory distress syndrome. Antiplasmin level was exceptionally high in about a fourth of the premature infants with or without respiratory distress syndrome. Plasminogen activator activity was found more often in the blood of infants with respiratory distress syndrome than in normal infants. This may be due to the liberation of tissue activators as a consequence of hypoxia. Because of the absence of the substrate (plasminogen), this activator level may have no significance. Tissue activator activity was found in the lungs of premature infants whether they died of hyaline membrane disease or from other causes. Forty-five infants with respiratory distress were treated in a therapeutic study. Twelve were treated in a preliminary series and 33 in a randomizd, double-blind investigation. Of the latter, 11 were treated with placebo, and 5 (45%) survived; 8 were treated with streptokinase activated human plasmin and 2 (25%) survived; 14 were treated with urokinase activated human plasmin and 12 (86%) survived. Among the infants who died, no definite hyaline membrane disease was found by histopathologic examination in two of the placebo group, one in the streptokinase-plasmin treated group, and the two who died in the urokinase-plasmin group. No significant side-effects of plasmin therapy were seen. Although considerable fibrinolytic and plasminogen-activator activity was generated in many treated patients, there was no significant fall in blood coagulation factors. Intracerebral hemorrhage, which appears to occur often in patients who die with hyaline membrane disease, was not more frequent in the plasmintreated group than in the placebo group.