The expression of hepatocyte growth factor (HGF) was studied in rat skeletal muscle during postnatal growth and during regeneration after ischemic injury. By Northern blot analysis two RNA transcripts with estimated sizes of 6.0 and 3.1 kb, respectively, could be detected in immature skeletal muscle at 2, 4, and 10 days after birth, whereas no signal could be detected in adult skeletal muscle. In regenerating muscle, HGF mRNA was reexpressed, and a distinct signal was evident during the first days after the injury. One week after the injury only a weak signal was obtained. By in situ hybridization staining, HGF mRNA could be demonstrated in the immature muscle tissue of newborn rats but not in adult skeletal muscle. In regenerating muscle, the staining for HGF mRNA could be demonstrated in the regenerating muscle cells during the early phase of the regeneration. One week after the injury, only faint staining for HGF mRNA persisted in the regenerated fibers. It is concluded that HGF expression is developmentally regulated in skeletal muscle and that HGF is reexpressed in a transient manner during postischemic muscle regeneration.