Since 1984, 11 newborns with severe respiratory distress have been treated whose clinical characteristics appear distinctive. Characteristics of these neonates were as follows: (1) they were full term by obstetric and neonatal criteria, (2) they had diffuse bilateral alveolar opacification on chest radiographs during the acute illness, (3) each had an acute perinatal triggering insult, (4) the neonates required continuous positive pressure ventilation for at least 48 hours with FiO2 greater than 0.50 for at least 12 hours, (5) they needed positive end-expiratory pressure of 6 cm of H2O or greater within three days of the triggering event, (6) there were no other known causes of these clinical conditions. Ten (91%) neonates had evidence of other organ dysfunction in addition to the lungs. Trials of hyperventilation in nine and tolazoline in five failed to improve oxygenation. Ten infants who underwent trials of increased positive end-expiratory pressure greater than or equal to 6 cm of H2O without other concurrent changes in ventilator settings responded with prompt increases in PaO2 (median increase 84 mm Hg, range 22 to 196 mm Hg). All 11 babies survived but required prolonged mechanical ventilation and supplemental oxygen. We suggest that adult respiratory distress syndrome can and does occur in newborns. A trial of positive end-expiratory pressure greater than or equal to 6 cm of H2O should be considered in full-term infants with severe respiratory distress in whom other causes can be excluded.