The number and distribution of bombesin immunoreactive pul-monary neuroendocrine cells (PNEC) in fetuses and infants up to 6 months of age was determined on postmortem lung specimens. Individual cells and clusters of cells (neuroepithelial bodies) were found in airways of all sizes, although greater than 95% of the positive cells were located in bronchioles, terminal bronchioles, and respiratory bronchioles. These infants were separated into two groups. In control infants, who died primarily from noncardi- opulmonary causes, bombsin immunoreactive neuroendocrine cells were identified throughout the latter half of gestation. As gestation advanced, progressively more positive bronchioles/cm2 of lung tissue and cells/bronchiole were identified. In these control infants, the number of positive bronchioles/cm2 and cells/bronchiole were at the highest level at or near the time of delivery and then gradually declined throughout the first 6 months of life. In contrast, infants who died of acute hyaline membrane disease (1-7 days of life) or bronchiopulmonary dysplasia (2 wk to 6 months of life) demonstrated marked differences in the number of identifiable bombesin immunoreactive neuroendocrine cells when compared to control infants. In early hyaline membrane disease, the number of positive bronchioles/cm2 and cells/bronchiole was markedly de-creased. During the transition to chronic bronchopulmonary dys-plasia, there appeared to be a marked increase in the number of bombesin immunoreactive cells. The peak number of cells occurred at 2-3 months of life, when substantially more bombesin-immu- noreactive cells could be identified in children with bronchopul-monary dysplasia than control infants of similar age Speculation: This study demonstrates that a specific pulmonary cell type containing bioactive molecules undergoes marked changes during acute and chronic neonatal lung disease. Anatomic and physiologic evidence suggests that these cells may be in an ideal position to exert control on pulmonary vessel and airway tone either at the local level or throughout the entire lung through vascular and neural connections. These data do not prove that alterations in this cell population are the cause of changes noted in airway and in vascular resistance in infants with lung disease. They do identify, however, a new area of potential investigation in these disease states.