Intensive exercise leads to a loss of force, which may be long-lasting and associated with muscle cell damage. In order to simulate this impairment and to develop means of compensating the loss of force, extensor digitorum longus muscles from 4 wk old rats were fatigued using intermittent 40 Hz stimulation (10 s on, 30 s off). After stimulation, force recovery, cell membrane leakage and membrane potential were followed for 240 min. 30-60 min of stimulation reduced tetanic force to around 10% of the prefatigue level, followed by a spontaneous recovery to around 20% in 120-240 min. The loss of force was associated with a decrease in K⁺ content, gain of Na⁺ and Ca²⁺ content, leakage of the intracellular enzyme lactic acid dehydrogenase (10-fold increase), and depolarization (13 mV). Stimulation of the Na⁺,K⁺-pump with either the ₂-adrenoceptor agonist salbutamol, epinephrine, rat calcitonin gene related peptide (rCGRP), or dibutyryl cyclic AMP improved force recovery by 40-90%. The -blocker propranolol abolished the effect of epinephrine on force recovery, but not that of CGRP. Both spontaneous and salbutamol-induced force recovery were prevented by ouabain. The salbutamol-induced force recovery was associated with repolarization of the membrane potential (12 mV) to the level measured in unfatigued muscles. In conclusion, in muscles exposed to fatiguing stimulation leading to a considerable loss of force, cell leakage and depolarization, stimulation of the Na⁺,K⁺-pump induces repolarization and improves force recovery, possibly due to the electrogenic action of the Na⁺,K⁺-pump. This mechanism may be important for the restoration of muscle function after intense exercise.