Excitation-transcription coupling, namely the process whereby plasma membrane depolarization leads to gene activation or inactivation, is still a black box for most muscle genes. Muscle regeneration is a useful model system to ask basic questions concerning the triggering signals and the transduction pathways involved in activity-dependent gene regulation. We report ongoing research in our laboratory concerning (1) myosin heavy chain changes in regenerating muscle in the presence and absence of the nerve, as well as changes induced by electrical stimulation, (2) identification of activity response elements in the promoter of a slow myosin light chain gene, and (3) potential approaches to define the transduction pathways induced by neural or electrical activity and implicated in muscle gene regulation.