Denervation of skeletal muscle stimulates increased turnover of muscle nuclei and connective tissue cells. The present investigation tests whether denervation "primes" myogenic precursor cells, so that the onset of DNA synthesis in muscle precursors after traumatic injury occurs earlier than in innervated muscle. The left legs of 29 male BALBc mice were denervated, and 1 week later small incisions were made in the tibialis anterior muscles of both legs (denervated and innervated). At specific times after injury each mouse was injected once with tritiated thymidine to label replicating muscle precursors. Muscle lesions were sampled 10 days after injury (when all precursors had fused to form myotubes) and prepared for autoradiography. The presence of labelled myotube nuclei showed that muscle precursors had been synthesizing DNA at the time when [3H]thymidine had been injected. Our data suggest that very few precursors were proliferating in denervated muscle within 30 h after injury, and the onset of myogenesis at 30 h was essentially the same in denervated and innervated muscle. The retrospective analysis indicates that there were also similar proportions of muscle precursors proliferating at different times after injury, in regenerating lesions of both denervated and innervated muscle. Thus, denervation does not stimulate an earlier regenerative response in injured skeletal muscle.