1. The sensitivity of the flexor digitorum longus and soleus muscles to depolarizing drugs was tested after cross-union of their respective motor nerves.2. The alien innervation did not affect the sensitivity of either the flexor digitorum longus (FDL) or soleus muscles, which retained their normal characteristic responses to decamethonium and suxamethonium. The time course of muscle contractions was, however, altered by the cross-union operation.3. A considerable increase in sensitivity to depolarizing drugs was shown after de-afferentation and after tenotomy of the soleus muscles. Both these conditions are associated with muscle atrophy.4. It is suggested that hypersensitivity to depolarizing drugs can be expected in any situation where the muscle is undergoing atrophy.