Human and mouse (C57BL/10SnJ+/+) myoblasts were injected separately in the muscles of C57BL/10SnJ mdx/mdx mice. Mouse myoblasts (C57BL/10SnJ+/+) were also injected in normal mice (C57BL/10SnJ+/+ and BALB/c +/+). Some muscles that received a xenotransplantation (i.e., human myoblasts) were previously injected with a myotoxin, i.e., notexin. This treatment was not used for the allografts (i.e., mouse myoblasts). Human myoblast injections did not increase the number of dystrophin‐positive cells above the background level due to backmutation. Moreover, the human myoblasts detected with an anti‐HLA antibody decreased rapidly during the 6‐week followup. The injection of normal mouse myoblasts in mdx mice did, however, increase the number of dystrophin‐positive fibers. Moreover, numerous cells expressing mouse MHC class II, macrophages, granulocytes, neutrophils, natural killer cells, and a subset of T lymphocytes were detected by immunohistochemistry in cryostat sections of myoblast injected muscles. These cells were present within 1 week of the myoblast injection in the muscle regions containing injected human or mouse myoblasts, and progressively decreased during the 6‐week follow‐up in the human myoblast transplantation. Lymphocyte infiltration reached a significant level following xeno‐ and alloincompatible transplantations. Antibodies against the human myoblasts and against alloincompatible myoblasts were also detected in the serum of the recipients. These results suggest that humoral and cellular immune reactions are responsible for the poor outcome of myoblast transplantation in mice and could be involved in failure of transplantation in Duchenne muscular dystrophy patients. These results indicate that adequate immunousuppression must be used in these patients.© 1995 John Wiley &Sons, Inc.