Cell surface alterations during myogenesis have been investigated in Yaffe's myogenic cell line L8, using indirect immunofluorescence with an antibody against the large external transformation-sensitive (LETS) protein. The immunofluorescent technique reveals a susbstantial alteration in the distribution of this surface antigen. With the prefused myoblasts, LETS protein is dispersed all over the cell surface; following myoblast fusion, this pattern is markedly changed. All of the fibril-like surface LETS protein disappears, and in some myotubes, discrete clusters of LETS protein become conspicuous. By use of radioimmunological assay, the total LETS protein is quantitatively reduced upon myoblast fusion.