Skeletal muscle fibers are capable of regeneration following ischemia, traumatic injury, or transplantation. Although the time course of the regenerative process has been studied in detail histologically, little is known about the time of activation of myogenic precursor cells which are primarily responsible for muscle regeneration. This study was designed to determine the initiation, peak proliferative activity, and cessation times of muscle precursor replication in small skeletal muscle transplants. Forty-eight young male BALB/c mice had the extensor digitorum longus muscles of both hind legs autotransplanted to a different site in the same leg. At various time intervals after transplantation (from 24 hours to 14 days), mice were injected once with a small dose of tritiated thymidine in order to label proliferating myogenic precursor cells. The transplants were allowed to regenerate for 14 days, before being removed, processed for autoradiography, and analysed by light microscopy. The presence of labelled myotube nuclei in regenerated transplants showed that myogenic precursors had been replicating at the time of tritiated thymidine injection. Myogenic precursor replication was initiated late on the second day (42-48 hours) after transplantation, peaked after 6 days, and was complete within 10 days.