Innervation has been generally accepted to be a major factor involved in both triggering and maintaining the expression of slow myosin heavy chain (MHC-1) in skeletal muscle. However, previous findings from our laboratory have suggested that in the mouse this is not always the case (30). Based on these results we hypothesized that neurotomy would not markedly reduced the expression of MHC-1 protein in the mouse soleus muscles. In addition other cellular, biochemical and functional parameters were also studied in these denervated soleus muscles to complete our study. Our results show that denervation reduced neither the relative amount of MHC-1 protein nor the percentage of muscle fibres expressing MHC-1 protein (p > 0.05). The fact that MHC-1 protein did not respond to muscle inactivity was confirmed in 3 different mouse strains (129/SV, C57BL/6 and CD1). In contrast, all of the other histological, biochemical and functional muscle parameters were markedly altered by denervation. Cross-sectional area (CSA) of muscle fibres, maximal tetanic isometric force, maximal velocity of shortening, maximal power and citrate synthase activity were all reduced in denervated muscles as compared to innervated muscles (p < 0.05). Contraction and half-relaxation times of the twitch were also increased by denervation (p < 0.05). Addition of tenotomy to denervation had no further effect on the relative expression of MHC-1 protein (p > 0.05) despite a greater reduction in CSA and citrate synthase activity (p < 0.05). In conclusion a deficit in neural input leads to marked atrophy and reduction in performance in mouse soleus muscles. However, the maintenance of the relative expression of slow MHC protein is independent of neuromuscular activity in mice.