Pulmonary interstitial emphysema (PIE) may occur spontaneously, as a complication of endotracheal tube displacement, intrauterine viral pneumonia or massive aspiration of formula. Nevertheless PIE occurs more frequently in neonates requiring mechanical ventilation for RDS. Untoward effects of large air collections in the extra-alveolar spaces are based on decreased perfusion and ventilation of the affected lung tissues, compression of adjacent pulmonary parenchyma and mediastinum, possible air embolism. Sometimes PIE spontaneously regress, but in some instances the process is self perpetuating, leading to an "air block syndrome". Fourteen (19.4%) of 72 infants ventilated for RDS in a three-year period had radiological evidence of PIE during the first few days of life. All 5 bilateral, 7 diffuse and 2 localized cases were treated with "vigorous pulmonary therapy". In addition to these procedures, 4 neonates were submitted to a selective bronchial intubation (SBI) and 5 different infants improved after HFV. No one of our patients underwent a surgical procedure. Infants with fine linear hyperlucencies improved sooner. All pneumothoraces (7 of 14) were preceded by X-ray appearances of PIE. Three neonates died. Mortality was observed in newborns with bilateral PIE, because of an intraventricular hemorrhage in two and an intractable under tension pneumothorax in one patient. Plain chest roentgenograms, histological pictures and treatment modalities of PIE remain separated from these considered for congenital lobar emphysema, congenital cystic adenomatoid malformation, bronchogenic cyst or lung sequestration. Surgical treatment of PIE is not as universally accepted as in congenital cystic lesions of the lung, in which it's mandatory.