The αvβ6 integrin was identified in cultured epithelial cells and functions as a fibronectin receptor. We have now used monoclonal antibodies to determine in vivo expression patterns of the β6 subunit in normal and pathological human or primate tissues, and during experimental wound healing or induced lung injury. The results indicate that β6 expression is restricted to epithelia and is up-regulated in parallel with morphogenetic events, tumorigenesis, and epithelial repair. During development of the kidney, lung, and skin, we found that β6 is expressed by specific types of epithelial cells, whereas it is mostly undetectable in normal adult kidney, lung and skin. In contrast, we detected high-level expression in several types of carcinoma. For example, β6 is almost invariably neo-expressed in squamous cell carcinomas derived from the oral mucosa, often focally localized at the infiltrating edges of tumor islands. Expression of β6 is also upregulated in migrating keratinocytes at the wound edge during experimental epidermal wound healing. Similarly, β6 expression is induced in type II alveolar epithelial cells during lung injury caused by injection of live bacteria. We also observed β6 expression in adult lungs and kidneys at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys. From these findings and earlier results, we hypothesize that αvβ6 affects cell spreading, migration and growth during reorganization of epithelia in development, tissue repair, and neoplasia.