Control of neonatal pulmonary vascular and airway resistance remains poorly understood. Recently, two additional intrapulmonary control systems, pulmonary neuroendocrine cells (PNEC) and the pulmonary peptidergic innervation (PPI), have been described, which may influence pulmonary vascular and airway tone in the neonate. PNEC are granulated cells that line the airways of fetal, neonatal, and adult lungs. They are particularly numerous in the neonatal period and contain peptides (bombesin, calcitonin, leu-enkephalin) and amines (serotonin) known to affect smooth muscle tone in other organ systems. The PPI, composed of fibers containing substance-P and vasoactive intestinal peptide (VIP), have been described in association with pulmonary airways and vessels of all sizes. Both these peptides are known to profoundly influence smooth muscle tone in other organ systems. Limited indirect anatomic and physiologic evidence has suggested a role for both systems in altering intrapulmonary smooth muscle tone, particularly in neonates; however, basic knowledge of both systems is extremely limited. The aim of this research program is to provide some of the fundamental knowledge necessary to assess the role of both these systems in influencing neonatal pulmonary vascular and airway tone under normal and pathologic conditions. This aim will be accomplished in the following fashion: (1) Determination of the development and distribution of PNEC and PPI within the lung using immunohistochemical techniques. (2) Determination of the anatomic distribution and number of receptors for the above peptides and amines, and their relationship to receptors for the presently characterized intrapulmonary control mechanisms (adrenergic and cholinergic innervation) using redioautography. (3) Determination of pathologic alterations in the structure and distribution of PNEC, PPI, and adrenergic, cholinergic, and peptidergic receptors in (a) experimental asthma and (b) acute and chronic neonatal cardiopulmonary disease where alterations in vascular and airway tone are either known to play a significant role (hyaline membrane disease, bronchopulmonary dysplasia, congenital heart disease) or may play a significant role (sudden infant death syndrome, cystic fibrosis). Should these two systems, pulmonary neuroendocrine cells and the pulmonary peptidergic innervation, influence neonatal vascular and airway tone; understanding their normal function and their alterations in common neonatal cardiopulmonary pathologic states may lead to novel therapies for a number of currently untreatable, or poorly treatabale, neonatal cardiopulmonary diseases.