Regeneration was studied in female Syrian golden hamster tracheal epithelium. The epithelium was focally removed in vivo by scraping it with a blunt probe. At 2 hours, virtually all cells had sloughed from the injured area leaving a bare basal lamina. At 6 and 12 hours, flattened cells that migrated from adjacent uninjured epithelium partially covered the denuded basal lamina. Increased cell division did not occur at these times. Many of the simple squamous cells contained well-developed endoplasmic reticulum, Golgi apparatus, and mucous granules. Other cells resembled basal cells. At 24 hours the defect was covered by one or two layers of simple squamous cells. At that time, many of those cells were in division, and cell division was also greatly increased in mucous cells and basal cells in the uninjured epithelium distant from the defect. At 48 hours the epithelium was stratified, composed of four or five layers of polygonal to flattened cells, typical of nonkeratinizing epidermoid metaplasia. The cells contained many tonofilament bundles, a large Golgi apparatus, and many tiny mucous granules. Mitoses were seen in all cell layers. At 72 hours, the surface layer of cells was undifferentiated (indifferent cells) overlying an epithelium that otherwise retained its epidermoid character. Indifferent cells were characterized by an electron-lucent cytoplasm and a lack of tonofilament bundles, mucous granules, or cilla. Cells similar in other respects to indifferent cells were seen that possessed mucous granules or early signs of cilla formation. Some cells showed mucous granules and cilla developing in the same cell. By 96 hours, the regenerated epithelium was fully differentiated and was indistinguishable from the normal epithelium. These observations show that mucous cells have a significant role in the regenerative response. Mucous cells have a dual potential; they can undergo epidermoid metaplasia and still retain the ability to secrete mucus. The study explains the universal occurrence of mucosubstances in areas of epidermoid metaplasia and makes more understandable the previously reported fact that many bronchogenic carcinomas are combined epidermoid and adenocarcinomas. In the presence of a carcinogen, the hypothesis has been forwarded that initiation of mucous cells and basal cells occurs, which leads to malignant transformation and produces tumors that show active secretory activity and keratinization, often in the same cell.