The purpose of this study is to examine the cellular and molecular events coincident with muscle denervation, especially the regenerative changes seen following muscle denervation, the role of satellite cells in this process, and the possibility of apoptotic degeneration of myonuclei as a mechanism of myonuclei loss during muscle denervation atrophy. Myosin heavy chain (MHC) isoform expression during muscle denervation was examined using pyrophosphate acrylamide gel electrophoresis and immunohistochemistry. DNA fragmentation (apoptosis) in myonuclei of denervated fibers was investigated using agarose gel electrophoresis, the TUNEL technique and ELISA for cytoplasmic histone-associated DNA fragmentation. Immunohistochemistry for MyoD and BrdU was also performed. Following muscle denervation, embryonic MHC, which is not expressed in adult healthy muscles, was expressed in some denervated fibers as well as in small activated satellite cells; maximal expression was observed 2 to 3 weeks after denervation. Activation and proliferation of satellite cells were observed, while few typical regenerating fibers were identified. It is speculated that most activated satellite cells fused to the denervated maternal fibers in order to repair them instead of fusing to each other to form new fibers as a mechanism that compensates for the atrophic changes after denervation. Although DNA ladder formation was not observed with agarose gel electrophoresis, DNA fragmentation was detected by the TUNEL technique and ELISA, suggesting that apoptotic degeneration contributes to the loss of myonuclei associated with denervation atrophy.