Bronchopulmonary dysplasia (BPD), the most common cause of chronic lung disease in prematurely born infants, is histologically characterized by various degrees of airway and alveolar septal fibrosis. Tryptase, serine protease specific to mast cells, has been shown to have potent fibroblast mitogenic properties and in addition has been shown to be increased in adult fibrotic lung disorders. Based on this analogy, the distribution of pulmonary mast cells exhibiting tryptase immunoreactivity was investigated by immunoperoxidase staining in autopsy specimens of infants dying with BPD. Morphologically normal lung specimens from similarly aged infants dying of sudden infant death syndrome (SIDS) served as controls. Tryptase–positive mast cell counts were performed at 250× from at least 10 random fields in bronchial, peribronchiolar, and alveolar regions. Compared to controls, in lung sections exhibiting typical histologic features of long‐standing BPD, tryptase positive cells were significantly increased in bronchial (23.9 ± 3.6 vs 14.4 ± 2.3) and peribronchiolar (15.3 ± 3.2 vs 4.63 ± 0.6) regions compared to controls (P < 0.05, Student's t test). In particular, alveolar regions exhibiting moderate to severe degrees of septal fibrosis exhibited dramatic increase in the number of tryptase‐positive cells (9.83 ± 1.89 vs 0.34 ± 0.18, P = 0.003). These findings of tryptase‐positive mast cell hyperplasia in BPD suggest potential roles of mast cells as well as tryptase in the pathogenesis of this disease. © 1995 Wiley‐Liss, Inc.