The pathogenesis of epithelial hyperplasia and squamous metaplasia of the tracheobronchial epithelium, induced by polynuclear hydrocarbons, was studied, with the Syrian golden hamster as a suitable animal model. The acute cellular changes in the tracheobronchial epithelium, produced by intratracheal instillations of benzo[a]pyrene carried by ferric oxide particles, included focal replacement of the columnar cells with pleomorphic cells. These had the ultrastructural features of atypical squamous cells, i.e., cytoplasmic filaments, widened intercellular spaces, abnormal desmosomes, and increased number of lysosomal derivatives. Polylobulated nuclei and pleomorphic nucleoli were prominent findings after multiple instillations of benzo[a]pyrene:ferric oxide. Intratracheal instillations of ferric oxide alone or pyrene:ferric oxide produced basal cell hyperplasia, which was reversible. The atypical squamous cells induced by benzo[a]pyrene:ferric oxide had ultrastructural features similar to hyperplastic epithelial cells described in the bronchi of smoking dogs and neoplastic squamous cells described in human bronchogenic carcinoma. This investigation is one of a series of studies to clarify the histogenesis of squamous cell carcinoma of the lung.