The clinical course of pulmonary interstitial emphysema (PIE), pneumomediastinum (PM), and pneumothorax (PT) was studied in 57 premature and 20 fullterm newborn infants. The results suggest that PIE, PM, and PT represent a continuum of a single process. Pneumomediastinum and PT without radiological evidence of PIE occurs with greater frequency in full-term infants, while PIE predominantly occurs in the preterm infant. Respiratory distress syndrome significantly increases the incidence of PIE. The presence of PIE was associated with a significant increase in mortality in the group of infants studied. In spontaneous cases a distinct clinical picture often precedes radiologic changes. This consists of barrel-shaped chest, retractions, tachypnea, and increased ambient oxygen requirements.