While numerous reports indicate that adult bone marrow-derived cells can contribute to nonhematopoietic tissues in vivo in adult mice, the generally low frequency of these events has made it difficult to study the molecular and cellular pathways involved. Here, we show a 1000-fold range in the frequency with which diverse skeletal muscles incorporate adult bone marrow-derived cells in adult mice. Most striking was the finding of one specific muscle, the panniculus carnosus, in which up to 5% of myofibers incorporated bone marrow-derived cells over a 16- month period in the absence of experimentally induced selective pressure. These results suggest that muscles differ physiologically, establishing the panniculus carnosus as an assay for identifying the key regulators, such as trophic, homing, and differentiation factors, as well as the relevant cells within the bone marrow that are capable of circulating throughout the periphery and contributing to adult, nonhematopoietic tissues, such as skeletal muscle. Finally, the 5% incorporation of adult stem cells into skeletal muscle is the highest reported to date in the absence of experimentally induced selective pressure and is at a level that may be consistent with improving the function of defective muscle tissue.