Muscle hypertrophy and tissue repair involves local as well as systemic growth factors. Using muscles that were stretched and/or electrically stimulated our team cloned an RNA transcript which has been called mechano growth factor (MGF) (Yang et al. 1996). This is a splice variant of the IGF-I gene but it has a reading frame shift, making its carboxy peptide sequence different from that of the systemic or liver type of IGF-I (IGF-IEa). In order to determine the role of MGF and particularly its unique C terminal peptide sequence in muscle maintenance we have studied certain disease states in which muscle mass is not maintained. It was found that dystrophic muscle cannot respond to mechanical stimuli by producing MGF in the same way as normal muscle. Also, studies in the muscles of old rats and elderly people have shown that the ability to produce MGF in response to resistance exercise declines markedly with age (Owino et al. 2001; Hameed et al. 2003). However, in the case of elderly people it is improved by the administration of growth hormone (Hameed et al. 2004). The function of MGF is illustrated by experiments using muscle cells in culture which have been transfected with the cDNA of MGF and of IGF-IEa. These have shown that the role of MGF, in particular its carboxy peptide, is to activate the proliferation of muscle satellite (stem) cells (Yang et al. 2002). This has now been shown to be true following muscle damage in vivo (Hill and Goldspink, 2003). IGF-IEa, which is also produced is the main supplier of ‘mature IGF-I’, but it is clear that the splice variant MGF has a separate and important role in replenishing the stem cell pool, which is important for muscle mass regulation and repair. MGF is much more potent than recombinant IGF-I or the systemic type of IGF-I in inducing hypertrophy as MGF apparently ‘kick starts’ the process by inducing proliferation of the satellite cells to provide the extra nuclei for the growth and/or repair of this post-mitotic tissue.