Following muscle damage in adult vertebrates, myofibers can be regenerated from muscle precursor cells (satellite cells). During this process, prenatal myogenesis is recapitulated to a large extent, both morphologically and molecularly. A putative morphoregulatory molecule involved in myogenesis is M-cadherin (Mcad), a calcium-dependent cell adhesion protein. The expression of Mcad was studied by immunofluorescence in regenerating, denervated, and normal mouse muscles. Our results demonstrate that Mcad is present in satellite cells in normal muscle. Enhanced staining at sites of contact between satellite cells and the parent muscle fiber suggests an additional, spatially restricted expression of Mcad in muscle fibers. Mcad positive cells in normal and denervated muscles did not incorporate bromodeoxyuridine within 24 hr after injection in vivo, indicating that Mcad is expressed on mitotically quiescent satellite cells. Neural cell adhesion molecule (NCAM) co-localized with Mcad in nearly all satellite cells in denervated muscles but rarely in intact muscles. At early stages of regeneration, Mcad was exclusively and strongly expressed in myoblasts. After fusion of myoblasts into myotubes, Mcad was down-regulated and was barely detectable on more mature myotubes surrounded by distinct basal lamina sheaths. These observations are in line with the idea that Mcad plays a crucial role in myogenesis. In intact muscle, Mcad might function as a molecular link between satellite cell and muscle fiber.