The effects of unloading on aged and young muscle have been well documented. However, the impact of unloading on the neuromuscular junctions (NMJs) of aged and young adult muscle has yet to be determined. PURPOSE The aim of this investigation was to assess the morphological plasticity of the NMJs of older and younger animals subjected to muscle unloading. METHODS Sixteen young adult (8 mo) and 16 aged (22 mo) male rats were assigned to either hindlimb suspension (HS), or control conditions (N=8/group) for a period of 4 wks. Following euthanization, soleus muscles were sectioned and stained using cytofluorescent procedures to visualize pre-synaptic acetylcholine vesicles and postsynaptic acetylcholine receptors. Images of NMJs were captured with a confocal microscope. Various aspects of pre- and post-synaptic NMJ morphology, including area and perimeter, were quantitated. RESULTS Among young adult rats, unloading failed to elicit significant alterations in either the pre-, or the post-synaptic components of NMJ morphology. In contrast, unloading among the aged rats resulted in significant (P < 0.05) increases in pre- and post-synaptic area (32% and 43%, respectively), and perimeter (15% and 17%). No significant differences in NMJ morphology were detected between young adult and aged control rats, i.e., no significant main effect of aging. CONCLUSION These data indicate that unlike young adult NMJs, the synapses of aged skeletal muscle undergo significant remodeling as a result of prolonged unloading. Importantly, these alterations cannot be ascribed to initial differences among aged and young adult control NMJs. Supported by NIH grant AG 1744C, and the Howard Hughes Medical Institute through a grant to The College of William & Mary.