Integrins are heterodimeric glycoproteins that mediate cell-to-matrix and some cell-to-cell interactions. Recent evidence underscores the important roles of these receptors in signaling machines that transduce positional information into complex changes in cell behavior. As such, integrins have been shown to play critical roles in cell growth, differentiation, and migration. Most cells express multiple members of this family, but the integrin repertoire of any given cell appears to be highly tissue- and cell-type-specific. We have used the homology-based polymerase chain reaction to identify known and novel integrin subunits in airway epithelial cells. With this technique we have identified three novel integrin subunits that participate in the formation of at least four novel integrin heterodimers. The best characterized of these, αvβ6, is a receptor for the extracellular matrix protein fibronectin, and appears to be expressed only in terminally differentiated mucosal epithelial cells. The novel a subunit, α9, forms a heterodimer with the known β subunit, β1, in some epithelial cell lines. Elucidatation of the specific roles these receptors play in airway health and disease will likely provide unique insights into both the biology of integrins and the biology of the airway epithelium.