A method of quantitating the airways amine precursor uptake decarboxylase (APUD) cells is proposed that relates these cells to total airway epithelial cells or airway length. In control rats, these values were 0.13 APUD cells/100 epithelial cells in the trachea, 0.03 in the large airways and 0.02 in the small airways. To evaluate the ability of this method to determine changes in number of APUD cells, rats were exposed to diethylnitrosamine (DEN) and nitrogen dioxide (NO2), which increase the number of airways APUD cells. The NO2 exposure was associated with a 2-fold increase in APUD cells of the trachea only without associated epithelial hyperplasia; DEN produced marked epithelial hyperplasia in the trachea and bronchi with a disproportionate increase in APUD cells in the bronchial epithelium only. The basis of this differential effect requires further study.