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Objective: To comprehensively evaluate complaints of muscle fatigue, weakness, and myalgias in Persian Gulf veterans (PGV). Background: Approximately 700,000 American troops were deployed to the Persian Gulf during Desert Shield and Desert Storm. Upon return from the Gulf, some PGV developed unexplained illnesses, and special referral centers were established for the evaluation of these patients. Among the most common symptoms of these PGV are fatigue, weakness, and myalgias. An Institute of Medicine committee recommended further exploration into the possible etiologies of these complaints. Methods: Twenty PGV with severe muscle fatigue, weakness, or myalgias that interfered with their daily activities were referred for an extensive prospective neuromuscular evaluation. Routine laboratory studies included serum creatine kinase (CK), erythrocyte sedimentation rate, thyroid function tests, and exercise forearm tests. All patients received nerve conduction studies (NCS), repetitive nerve stimulation, quantitative and single-fiber electromyography (EMG), and muscle biopsies. Results: Manual muscle strength examinations were normal in all patients. Six patients had mildly elevated CKs (range 223 to 768 IU/l); otherwise, laboratory tests were unremarkable. NCS were normal except in 2 patients with carpal tunnel syndrome. Quantitative EMGs were normal. One patient had mildly increased jitter on single-fiber EMG. Muscle biopsies demonstrated minor nonspecific abnormalities in 5 patients (i.e., increased central nuclei, rare necrotic fibers, tubular aggregates). Conclusions: Despite severe subjective symptoms, most of our patients had no objective evidence of neuromuscular disease. Mildly increased CKs or nonspecific histologic abnormalities on muscle biopsy were evident in 8 patients but were not believed to be clinically significant in most. We found no evidence of a specific neuromuscular disorder in any patient. Exposures to toxins during the Persian Gulf War were not likely responsible for our patients’ symptoms.