Immature and mature rabbit neonates were observed for production of intrapulmonary foam during the first 5–10 min of extrauterine life. Viability at birth of littermates was determined. In addition, lungs from neonates that had breathed 3–5 min after birth and from fetuses that had not breathed were studied during manual inflation to maximal volume and deflation to zero trans-pulmonary pressure (minimal volume). Lung wet/dry weights and amniotic fluid lecithin-to-sphingomyelin ratios were determined. Compared with mature subjects, body weights and lecithin-to-sphingomyelin ratios were significantly lower in the immature group, and total water content was significantly higher. No immature neonate lived to 3 hr, whereas all mature neonates were robust, active, and normal. Both spontaneous breathing up to 10 min and manual inflation-deflation were associated with intrapulmonary foam in each mature lung, but with little or no foam in immature lungs. The following were characteristic of immature lungs: 1) Airways and terminal lung units (TLU) were generally liquid-filled at zero transpulmonary pressure. 2) When lungs were inflated to maximal volume, all TLU appeared aerated. 3) However, during deflation liquid refilled most TLU and airways and >95% of the air previously introduced was returned to the syringe. 4) Air trapped in TLU at end deflation was not due to airway collapse, but to relatively early refilling of more proximal adjacent airways which thereby prevented air from leaving more peripheral TLU. Similar studies of mature lungs confirmed our previous report (Pediatr. Res.,I2: 1070 (1978)) that intrapulmonary foam is produced at the onset of breathing at birth and, also, during initial manual inflations of the liquid-filled fetal lung. Thus, the striking difference between the mature and immature lungs is the inability of the latter to produce foam. This is related to immaturity of the surfactant system, inability to establish residual volume at the onset of breathing, and retention of liquid in potential air spaces.SpeculationImmaturity of the surfactant system inhibits the production of intrapulmonary foam at the onset of air-breathing at birth. This deficiency, which is characteristic of immature lungs, retards residual volume formation and fetal pulmonary fluid absorption. Therefore, pulmonary blood flow, gas exchange, and alveolar lining formation are compromised.