Normal human myoblasts were cloned and transplanted in the tibialis anterior of immunodeficient nude and SCID mice and in mdx mice under different immunosuppressive treatments (cyclosporine A, CsA; antilymphocyte serum, ALS) or not immunosuppressed. This permitted us to show the interaction of the immune system in the myoblast transplantation. The graft success was assessed by verifying signs of humoral and cellular immune reactions and the presence of dystrophin produced by the fusion of the donor myoblasts. This study showed that clones of human myoblasts were able to fuse and produce dystrophin in injected muscles of immunodeficient mice and mdx mice receiving an effective immunosuppressive treatment (i.e., ALS+CsA). However, the same pool of human myoblasts injected in mdx mice inadequately immunosuppressed (i.e., CsA alone or ALS alone) triggered an immune reaction and was rejected. Cells expressing CD4 and CD8 antigens were observed in the injected muscles of mice treated with CsA alone. Therefore, evidence of humoral and cellular rejection was observed following human myoblasts transplantation.