Objective. —To determine the adverse effects of pretreatment with pyridostigmine bromide for nerve agent exposure during wartime. Design. —A retrospective study. Setting. —Southwest Asia. Participants. —Personnel who provided medical support to the XVIII Airborne Corps. These medical officers supplied information pertaining to symptoms and disposition of 41 650 soldiers who received pyridostigmine at the onset of hostilities of Operation Desert Storm. Intervention. —Pyridostigmine bromide, 30 mg orally, was self-administered every 8 hours while under the threat of nerve agent attack (for 1 to 7 days). Main Outcome Measure. —Physiologic changes attributable to pyridostigmine that resulted in need for medical attention, discontinuation of the drug, hospitalization, and/or evacuation from Southwest Asia. Results. —About half of the population noted physiologic changes that were not incapacitating, such as increased flatus, abdominal cramps, soft stools, and urinary urgency. Approximately 1% of the soldiers believed they had effects that warranted medical attention, but fewer than 0.1% had effects sufficient to discontinue the drug. Nonincapacitating symptoms often occurred; however, military mission performance was not impaired. Conclusion. —While under the threat of nerve agent attack, pyridostigmine can be administered to virtually all soldiers. (JAMA. 1991;266:693-695)