Integrins are a major family of cell adhesion molecules involved in cell-cell and cell-extracellular matrix interactions. Each integrin is a heterodimeric glycoprotein composed of an α and a β subunit. We now report the cDNA sequence and distribution of a new human integrin α subunit. This sequence is 78% identical to the previously reported chicken α₈ integrin sequence. Thus, we have designated this subunit as human α₈. By northern blot analysis, an α₈ probe detects two mRNA species of approximately 6.5 and 4.0 kb in neuroglioma H4 cells. An anti-α₈ polyclonal antibody precipitates a protein complex containing the β₁ subunit associated with the putative α₈ subunit, which has an apparent molecular mass of 180 kDa (non-reduced) or 155 kDa and 25 kDa (reduced). Immunohistochemistry with anti-α₈ polyclonal antibody in adult rat tissues shows prominent staining in vascular and visceral smooth muscle. In addition, the antibody strongly stained kidney mesangial cells and a cell type in the alveolar wall of the lungs, most likely corresponding to alveolar myofibroblasts. These results suggest that in adult mammalian tissues, α₈ is predominantly expressed in smooth muscle and smooth muscle-like contractile cells.