In the conditions of chronically elevated glucocorticoid agents in plasma, a drop in AChE activity of about 45% was reported. This data suggests the possibility that among other factors glucocorticoids also control AChE activity in the skeletal muscles. The question addressed in the present investigation was if AChE activity was reduced uniformly or selectively in the rat skeletal muscles after chronic application of dexamethasone? Selective effects of glucocorticoids on the AChE activity in different muscles and/or different types or regions of muscles would suggest the potential of these agents to regulate AChE metabolism in the skeletal muscle according to the environmental demands. Specific activity of skeletal muscle AChE was reduced in sternomastoideus (SM), extensor digitorum longus (EDL) and diaphragm (D) but not in soleus (SOL) after chronic dexamethasone treatment. Axial SM (white part) was more affected than distal white muscle EDL. AChE was better preserved in red rather than in white parts of muscles. The endplate-free region lost twice as much of specific AChE activity than the endplate-rich region. Our results suggest, but do not prove that glucocorticoid agents act in a selective way on the AChE metabolism of the skeletal muscles.