Increases in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells have been documented in infants with bronchopulmonary dysplasia. As some of the secretory products of these postulated airway chemoreceptors are known to adversely affect pulmonary vasomotor and bronchomotor tone, the present study was undertaken to determine if similar changes occur in the lungs of older pediatric patients with chronic respiratory disease. Immunoreactive cells were identified using the antibody-peroxidase-antiperoxidase technique and expressed as immunoreactive bronchioles/cm2 of lung tissue. In subjects dying an accidental or noncardiopulmonary death (control group: n = 48, zero to 24 yr of age), the total number of bombesin, calcitonin, and serotonin immunoreactive bronchioles/cm2 was greatest at birth, then decreased rapidly to extremely low levels after the first year of life. In the cystic fibrosis (n = 55, 3 days to 29 yr of age) and prolonged ventilation (n = 24, 4 months to 18 yr of age) groups, there was a significant increase (p<0.035) in bombesin, calcitonin, and serotonin immunoreactive bronchioles/cm2 from 1 to 11 yr of age. In the cystic fibrosis group, there was a sixfold increase in the number of serotonin immunoreactive bronchioles/cm2 lung tissue (p<0.015) compared with that in the other 2 groups during the first decade of life, suggesting a response to specific factors present only in the lungs of patients with this disease. In all 3 groups, immunoreactive cells were infrequently identified after 11 yr, implying a fundamental change in neuroendocrine cell biology coincident with the termination of lung growth and/or the onset of puberty. This study identified distinct changes in a pulmonary cell line known to elaborate peptides and amines with positive and negative effects on pulmonary function in older pediatric patients with chronic lung disease, and suggests that these cells and their products continue to offer a promising area for investigation in pediatric pulmonary diseases.