Clara cell 10-kDa protein (CC10) is an inhibitor of phospholipase A₂ and binds to phosphatidylinositol. It may therefore interfere with intracellular signal transduction. Bronchial CC10-reactive cells have been described by several authors. In contrast to the bronchiolar CC10-containing Clara cell, which is a progenitor cell of terminally differentiated airway epithelium, the role of bronchial CC10-reactive cells remains to be elucidated. We assessed the number of bronchial CC10-reactive cells in relation to cytokeratin (CK) expression and proliferative activity in normal, hyperplastic and squamous metaplastic epithelium. Sixty-five human bronchial mucosal specimens were investigated immunohistochemically for CK expression (CK7, CK13 and CK5/6), proliferative activity (MIB-1) and number of CC10-reactive epithelia. The proliferation fraction of CC10-reactive cells was assessed with double staining for MIB-1 and CC10. The proliferation index of the epithelium differed significantly between normal, hyperplastic and metaplastic epithelium. The number of CC10-reactive cells was inversely related to the epithelial proliferation. Bronchial CC10-reactive cells showed no proliferative activity as assessed using immunohistochemical double staining for CC10 and MIB-1. In contrast to normal and hyperplastic epithelium, squamous metaplasia disclosed CK5/6 in all epithelial layers, a loss of CK7 and a gain of CK13. We conclude that CC10-reactive cells have no progenitor role in the bronchial mucosa. However, because the proliferative activity is inversely related to the number of CC10-reactive cells, the CC10 protein may play a role in the regulation of epithelial repair. Squamous metaplasia most likely originates from basal cells.