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In this study, the authors describe 2 patients who experienced confirmed exposures to anticholinesterases that commenced in the 1970s. Subsequently, elevations in creatine phosphate kinase (CPK) were initially detected more than a decade following the first acute exposure. Beginning in the early 1980s, the patients suffered from progressive generalized muscle weakness, chronic fatigue, myopathy, neuropathy, and severe neurobehavioral impairments. Previous occupational exposures included pyridostigmine, as well as isopropyl methylphosphonofluoridate (percutaneous lethal dose [LD50] < 28 mg/kg body weight), and 1 patient had exposure to agricultural organophosphates. The authors hypothesize that the workers' CPK elevations, first detected more than a decade following acute exposures to anticholinesterases, were sentinel events for impending muscle damage and necrosis. Many Gulf War veterans with Gulf War disease who reported exposures to anticholinesterases 1 decade earlier currently suffer from vague neuromuscular and cognitive impairments. Therefore, medical programs for Gulf War veterans with Gulf War Syndrome should include surveillance for elevated CPK, abnormalities of neuromuscular conduction, and genetic susceptibility, and they should promote therapeutic trials for palliation.