Objective: The skeletal muscle cells are the largest cells in the mammalian body, and are one of few syncytia in mammals. Both in man and in animals it has been widely accepted that muscle cell size is correlated, and perhaps even causally related, to the number of myonuclei. Thus, it is assumed that hypertrophy involves incorporation of new nuclei from satellite cells, and that atrophy involves loss of nuclei by apoptosis. Methods: Mice were denervated or neural transmission was blocked using TTX for up to 24 days, and stained in vivo using either intracellular injection of fluorescent oligonucleotides, or transfection with a plasmid encoding EGFP with a nuclear localization signal. Apoptotic nuclei were detected using TdT-labeling of fragmented DNA. Results: After denervation up to 24 days there was no loss of myonuclei in neither the EDL nor solei muscles. We found the number of myonuclei per mm to be 52.95±1.7 (before denervation), vs. 54.31±2,8 (after denervation) in the EDL, and in the soleus 71.94±2.9 vs. 74.56±3.9, in spite of a reduction in cross sectional area of more than 50%. TTX block of the sciatic nerve yielded similar results. Apoptotic nuclei were found in the atrophying muscle tissue, but none of these were identified as belonging to muscle fibers. Conclusion: The classical idea of a constant karyoplasmatic ratio cannot be maintained for denervation atrophy. We confirm that in the first period after denervation, muscle tissue is undergoing atrophy and an active period of apoptosis, but the loss of cell nuclei by apoptosis seems to be confined to stroma and satellite cells.