Central nervous system (CNS)-induced suppression on the muscle Na-pump activity was studied in soleus (SOL) muscles of hypokalemic rats. Peripheral nerve section, cervical soleus and brainstem transection, decerebration, and cortical spreading depression with 20% KCl activated the Na-pump in SOL muscles during hypokalemia. Blockage of the nerve conduction by tetrodotoxin (TTX) also activated the Na-pump in SOL muscles. The activation of Na-pump after the denervation was completely abolished by the pre-treatment of ouabain. However, the muscle cation contents were not affected by the injection of curare and atropine. The activation of Na-pump in the muscles after denervation in the curarized hypokalemic rats was completely removed by electrical stimulus of the distal nerve stump of cut sciatic nerve. alpha-Adrenoreceptor antagonists (phenoxybenzamine, phentolamine and dibenamine, and prazosin) stimulated the Na+ and K+ transports in the SOL muscles during hypokalemia while beta-adrenoreceptor antagonist (propranolol) had no effect. The denervation effect on SOL muscle cation contents was not affected with or without the presence of propranolol. It is concluded that CNS acts to inhibit the Na-pump mechanism in SOL muscles of hypokalemic rats and the inhibition is achieved by the apparent release of catecholamines onto muscle following neural activity. Thus, the CNS-induced suppression on the muscle Na-pump is prevented by denervation and by treatment with drugs that block either nerve conduction or alpha-adrenoreceptor.