Ten critically ill newborn infants presenting with documented septicemia were treated with antibiotics and supportive measures that included assisted ventilation, large blood transfusions and other volume expanders, sodium bicarbonate, and vasoactive drugs. Upon failure of the above treatment to improve the infants' rapidly deteriorating condition and the development of sclerema, exchange transfusions with fresh whole blood were performed and repeated up to four times. Seven of the ten infants showed immediate improvement and ultimately survived. IgM and IgA rose consistently with exchange transfusions. We postulate that these infants improved following exchange transfusion as the result of the removal of endotoxins, improvement of perfusion and of tissue oxygenation, decrease of hemorrhagic complications, and enhancement of the humoral and cellular inflammatory response. The development of sclerema in septicemic newborn infants continues to be an ominous sign despite the use of antibiotics and supportive measures. Our data suggest that exchange transfusions decrease the mortality of this group of critically ill infants.