The purpose of the study was to determine the role of excitation-contraction coupling in the increased endurance time for low-force contractions after 4 weeks of elbow joint immobilization. Twelve subjects participated in a protocol that required immobilization of the elbow joint in a fiberglass cast for 4 weeks, and 4 subjects acted as controls. Measurements of muscle strength, contractile properties, and fatigability were performed before and after 4 weeks of limb immobilization, and after 4 weeks of recovery. The immobilization intervention produced significant reductions in the daily activity of the elbow flexor muscles, a 21% decline in the maximum voluntary contraction (MVC) force, and a 31% decrease in the maximum load that could be lifted once. Seven of the immobilized subjects exhibited an unusual pattern of muscle activity during the fatiguing contraction after immobilization, which was associated with an increase in the endurance time of the elbow flexor muscles (mean = 220%) in these subjects. The unusual pattern of muscle activity involved lower relative activity of the brachialis muscle, no increase in the amplitude of the electromyogram (EMG) for the elbow flexor muscles, and intermittent rather than continuous EMG. In contrast, the force-frequency relationship of biceps brachii was not altered by immobilization in these subjects, suggesting that adaptations in excitation-contraction coupling were not the primary cause of the prolonged endurance time after immobilization. Rather, the results suggest that the prolonged endurance time exhibited by some subjects after immobilization was largely due to adaptations within the nervous system.