Persistent pulmonary hypertension of the newborn (PPHN) is one of the most challenging situations in the neonatal intensive care nursery and it is associated with a high mortality rate. Hyperventilation therapy has been recommended as the primary ventilator management during recent decades. The associations of pulmonary barotrauma, chronic lung disease and hearing impairment raised the questions of significant pulmonary and neurological complications with this therapeutic modality. From July 1990 to April 1993, 14 cases of neonatal persistent pulmonary hypertension were treated with nonhyperventilation respiratory therapy at the Chang Gung Memorial Hospital. The goals of this therapy were to attain a pH level between 7.40 and 7.50, a PaO2 level between 60 and 90 mmHg and a PaCO2 level between 30 and 50 mmHg. High peak inflating pressure (> 35 cmH2O) and high ventilator rates (> 60/min) were avoided. The average duration on a ventilator was 6.8 +/- 2.9 days. Four patients had pulmonary barotrauma (29%); three of which were pulmonary interstitial emphysema and one pneumothorax. Three patients died (21%). Only one patient had neurological sequelae. No one had developed chronic lung disease. The non-hyperventilation approach for PPHN may be considered as an alternative ventilator management before starting a more aggressive hyperventilation therapy.