Abstract Cadherins belong to a large family of membrane glycoprotein adhesion receptors that mediate homophilic, calcium-dependent cell adhesion. During myogenesis, cadherins are involved in initial cell-to-cell recognition; and it has also been suggested that they play a role in the initiation of myoblast fusion into multinuclear myotubes. One of the members of the cadherin family, M-cadherin, has been detected during embryogenesis in myogenic cells of somitic origin and in adult muscles. We investigated the distribution and function of M-cadherin and β-catenin during differentiation of myoblasts in primary cultures of rat satellite cells. We found that M-cadherin was accumulated at the areas of contact between fusing myoblasts and that it colocalized with β-catenin. Moreover, β-catenin colocalized with actin in pre-fusing myoblasts. We show that myoblast differentiation is accompanied by an increase in the amounts of M-cadherin and β-catenin both at the mRNA and the protein level. Flow cytometry analysis showed that M-cadherin expression was highest in fusing myoblasts. In addition, an antibody specific for the extracellular domain of M-cadherin inhibited the fusion of cultured myoblasts. These data suggest that regulation of the M-cadherin level plays an important role in the differentiation of satellite cells and in myoblast fusion in primary cultures.