To determine how and when the satellite cells are stimulated to replicate in muscle regeneration, the rat soleus muscle was examined chronologically after bupivacaine-induced myonecrosis. Bromodeoxyuridine and desmin-positive mononuclear cells, indicating the start of satellite cell replication, were seen 25 h after bupivacaine treatment when macrophages had already invaded the sarcoplasm of necrotic fiber. These findings suggest that muscle regeneration starts as early as the time at which macrophages begin to scavenge necrotic material. Proliferating myoblasts increased in number, reaching a maximum at 49 h after myonecrosis, and decreased in number 3 days after the myoblasts fused with each other form myotubes. The satellite cell proliferation after bupivacaine-induced myonecrosis began at almost the same time as in crush injury, and earlier than after muscle transplantation using whole intact or minced muscle fragments. The earlier beginning and more rapid regenerating process probably resulted from the preservation of intact satellite cells, blood vessels and peripheral nerves in the bupivacaine-induced myonecrosis.