A 33-year-old man with a history of recreational benztropine abuse presented to the emergency department with confusion, abdominal pain, and distention. An abdominal radiograph revealed gross fecal loading. He was initially treated with intravenous fluids and opiate analgesia. Subsequently, a diagnosis of anticholinergic poisoning was made, based on tachycardia, delirium, dry mucosa, and reduced bowel sounds. Treatment with tacrine reversed the delirium, and a history of repeated benztropine use was obtained. Persistent ileus was treated with repeated doses of neostigmine, and gastrointestinal motility returned with prompt defecation. Neostigmine appears to be useful in reversing ileus caused by anticholinergic drug overdose. Theoretically, it may be useful in reversing anticholinergic ileus resulting from acute drug overdose, allowing or enhancing decontamination, but the safety and potential efficacy of neostigmine in this scenario have not been established.