We reviewed the clinical courses of 12 prematurely born newborns who were placed in continuous negative pressure (CNP) in an Isolette negative pressure ventilator for refractory hypoxemia while receiving intermittent positive pressure mandatory ventilation. All patients had severe lung disease as documented by an increased oxygenation index and bilateral pulmonary interstitial emphysema on x-ray examination. Patients were separated into two groups--survivors and nonsurvivors, with six patients in each group. Initiation of CNP resulted in a significant initial improvement in oxygenation in both groups seen as a 52% decrease in the oxygenation index in survivors and a 57% decrease in the oxygenation index in nonsurvivors (P less than .05). The survivors characterized themselves by showing a further sustained improvement in the oxygenation index--31.4 +/- 9.1 to 6.9 +/- 5.0 (P less than .01)--and a significant decrease in the mean airway pressure--11.6 +/- 4.6 cm H2O to 5.0 +/- 1.9 cm H2O (P less than .05). Four of the six survivors showed radiographic resolution of pulmonary interstitial emphysema. CNP was initiated at a mean age of 68.3 hours in the survivors. Nonsurvivors were initiated in CNP at a mean age of 134.3 hours, but went on to clinically deteriorate owing to irreversible hypoxemia and acidosis. Both oxygenation index and mean airway pressures were virtually unchanged compared with their initial values. The exact mechanisms by which CNP improves pulmonary function in this group of infants is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)