Three types of nonciliated secretory epithelial cells are thought to contribute to the mucous lining of intrapulmonary airways: mucous cells, serous cells, and Clara cells. The Clara cell is distinguished from the other two by low cuboidal shape, presence of membrane-bound electron-dense ovoid secretory granuLes, abundant apical agranular endoplasmic reticulum (AER), and its location as the lining cell of distal conducting airways (bronchioles). The present study was designed to define the distribution of the Clara cell within the trachea and intrapulmonary airway tree. We correlated airway size, generation of branching, and airway wall components with Clara cell morphology and abundance. Lungs of 6 male rabbits (8-15 weeks old) free of respiratory disease were fixed by airway infusion of glutaraldehyde/paraformaldehyde at 30 cm pressure. The trachea, primary bronchi, and airways of the right cranial lobe of each lung were exposed by microdissection. The branching pattern was recorded and numbered. One half of the dissected lung was processed for scanning electron microscopy and the other half embedded as large epoxy blocks for simultaneous transmission electron and light microscopy. The percentages of ciliated, mucous, nonciliated, and basal epithelial cells were quantitated by light microscopy. Basal cells and peribronchial cartilage were absent distal to the fourth intrapulmonary generation in both the axial airway and its first major branch. Mucous (goblet) cells were present (less than 2%) only in trachea and primary and lobar bronchi. Nonciliated cells were more abundant distally, constituting 21%-45% of the epithelium in cartilaginous airways and 35%-65% in noncartilaginous ones. In the first six airway generations including trachea, nonciliated cells were without large apical protrusions but were covered by long microvilli. Cells of more distal airways had prominent apical protrusions and lacked microvilli. Nonciliated cells in all airways had abundant apical AER, granular endoplasmic reticulum (GER), and electron-dense ovoid granules. Cells in proximal airways were columnar rather than low cuboidal and had more GER. Only nonciliated cell shape, luminal surface, and granule abundance varied with airway size and generation. We concluded that the nonciliated secretory cell lining all intrapulmonary airways in the rabbit lung is one cell type, the Clara cell.