K depletion leads to a selective loss of K from skeletal muscles, which is associated with a decrease in the number of [3H]ouabain binding sites. The significance of the nerve supply for these changes has been assessed in denervation experiments with K‐depleted rats. In K‐depleted rats (age 4‐12 weeks) denervation led to a partial recovery of the K contents in soleus (46‐77%), gastrocnemius (23%) and extensor digitorum longus (e.d.l.) muscles (19%) within 24 h. These effects were not prevented by beta‐adrenoceptor blockade or mimicked by alpha‐adrenoceptor blockade. In K‐depleted rats the number of [3H]ouabain binding sites was not increased following denervation. In K‐depleted rats 24 h of plaster immobilization of the entire hind limb caused 51% recovery of the total K content in soleus, whereas gastrocnemius and e.d.l. showed 49 and 16% recovery, respectively. Tenotomy for 3 h caused a rise in total K content of 33% in soleus muscles from K‐depleted rats. Anaesthesia for 3 h increased the total K content by 23%. The recovery of K induced by denervation, immobilization in plaster, tenotomy or anaesthesia was associated with an equivalent decrease in Na content. Denervation performed before K depletion reduced the loss of K from soleus, but not from gastrocnemius and e.d.l. In both soleus and e.d.l. the number of [3H]ouabain binding sites, however, decreased to the same level as in the contralateral innervated muscles. Denervation reduced, but did not prevent, the increase in the number of [3H]ouabain binding sites seen after re‐administration of K to K‐depleted rats. It is concluded that the changes in Na‐K contents seen after denervation in K‐depleted rats are the outcome of cessation of muscle activity. The results give no support to the idea that the effects of K depletion on the K content and the number of [3H]ouabain binding sites in skeletal muscle are mediated by the peripheral nerves.