The ADAMs (A Disintegrin and Metalloprotease Domains) are a family of membrane-anchored proteins that play a role in fertilisation, myoblast fusion and ectodomain shedding of cell surface proteins. Meltrin γ (ADAM-9) is a widely expressed member of this family and is involved in the shedding of heparin binding epidermal growth factor. Here we report that meltrin γ can function as a cell adhesion molecule via its disintegrin domain. Using solid-phase binding assays and antibody inhibition experiments, we demonstrate that a murine meltrin γ-Fc (Melγ-Fc) fusion protein binds to the integrin α₆β₁ on the surface of fibroblast cell lines, HT1080 and Wehi 164 in a specific manner. Since α₆β₁ is important for the motility of several cell types on laminin, cell migration studies using time-lapse video microscopy were performed. Cells adhering to Melγ-Fc displayed a rounded morphology and a marked increase (eight-to tenfold) in their motility compared to that on laminin. Furthermore, the p160 ROCK kinase inhibitor Y-27632 specifically reduced the migration of cells on meltrin γ but had no effect on migration of cells on laminin, whilst the general tyrosine phoshorylation inhibitor, genistein, inhibited cell migration on both substrates. These results together suggest that meltrin γ may play a role in regulating the motility of cells by binding to α₆β₁ integrin and this may be important during a variety of biological and pathological processes.