We examined the direct effects of the commonly used immunosuppressive agents cyclosporin A and cyclophosphamide on cultures of clonally derived aneural human myoblasts. When applied to cultures in doses reflecting the therapeutic dose in vivo, both cyclosporin A and cyclophosphamide had dose-related reproducible effects on myoblast fusion: fusion was enhanced by cyclophosphamide and inhibited by cyclosporin A. These findings indicate that immunosuppressive agents may have effects on muscle that are independent of their ability to regulate the immune system.