BACKGROUND Chronic exposure to glucocorticoids affects both the structure and function of vertebrate skeletal muscles. As little is known about the effects of such steroids on the neuromuscular junctions (NMJs) of different muscle fiber types, the influence of chronic corticosterone (CORT) administration on the ultrastructure of NMJs of soleus (SOL) and extensor digitorum longus (EDL) was studied. METHODS Ten Fischer 344 male rats, the same animals used previously, were either injected daily with 5-10 mg CORT or received vehicle as control animals for 3 months and were sacrificed at 5 months of age. Muscles were bathed in situ in 4% phosphate buffered glutaraldehyde for ten minutes, then removed and conventional electron microscopic procedures were followed. Qualitative and quantitative observations of nerve terminal ultrastructures were statistically treated with multivariate analysis of variance to determine differences between control and CORT-treated animals. RESULTS Fast-twitch EDL muscles were more affected by CORT-treatment than slow-twitch SOL muscles. Morphometric analysis of NMJ's in CORT-treated rats revealed significant decrease in fiber diameter, nerve terminal area and synaptic vesicle density, but a significant increase in synaptic cleft (P < 0.05). The NMJ's underwent partial denervation and reinnervation processes as demonstrated by large areas of presynaptic nerve terminal occupied by microtubules and electron dense granular material. CONCLUSIONS Chronic CORT-treatments induced degenerative changes which were more pronounced in fast-twitch EDL muscles than slow-twitch SOL muscles, suggesting that pattern or amount of activity affect the CORT-treatment outcome. These steroid-induced stress changes are similar to those observed in aging and disuse studies of NMJ. Thus, glucocorticoid hormones may play an etiological role in the homeostasis of the NMJ in response to various stimuli.