Replicating chicken embryo myoblasts were treated with a monoclonal antibody, CSAT, which recognizes and blocks the function of the beta subunit of integrin. In the presence of this antibody, myoblasts continued to replicate and did not fuse or produce muscle-specific meromyosin. This block to normal differentiation was readily reversed by the removal of the antibody. The reversed cells exhibited increases in desmin and meromyosin, and fused to produce contracting myotubes. The data indicate that the interaction of integrin, present on the membrane of replicating myoblasts, with extracellular matrix on the substrate is essential to initiate the terminal stages of myogenic differentiation.