Treatment of severe iron overdose in two children is described, and the pathophysiology of iron toxicity and management of acute iron poisonings are reviewed. An 11-month-old boy was comatose and in shock several hours after ingesting approximately 50 ferrous sulfate tablets (elemental iron 390 mg/kg). He had hyperglycemia and leukocytosis. Lavage was performed with a solution containing deferoxamine and sodium bicarbonate, and deferoxamine was given by continuous i.v. infusion for 48 hours. The initial serum iron (SI) concentration of 14,250 micrograms/dL decreased to 657 micrograms/dL nine hours after i.v. deferoxamine therapy was initiated. A roentgenogram showed tablets in the stomach and small bowel. Packed red blood cells were administered to treat apparent necrotizing gastroenteritis. SI concentration returned to normal by day three [corrected], and the child recovered. A 2.5-year-old boy was examined 1.25 hr after ingesting an estimated 55 tablets of ferrous gluconate 325 mg (elemental iron 130 mg/kg). Initial SI concentration was 134 micrograms/dL, and total iron-binding capacity (TIBC) was 219 micrograms/dL. A roentgenogram indicated iron concretion in the stomach and iron tablets in the small bowel. He underwent lavage with solution containing sodium bicarbonate. An i.m. dose of deferoxamine was administered, followed by i.v. deferoxamine therapy. SI concentration eight hours after the ingestion was 290 micrograms/dL, and whole-bowel irrigation was begun with polyethylene glycol-electrolyte solution. The irrigation and deferoxamine therapy were discontinued 20 hours after the ingestion, when SI concentration was 73 micrograms/dL, and the child recovered. Acute iron ingestions of more than 60 mg/kg are potentially serious. Patient 1 had severe iron intoxication, while aggressive treatment prevented severe toxicity in patient 2. Acute iron toxicity includes effects on the GI tract and the cardiovascular, metabolic, hepatic, and central nervous systems. Guidelines for assessing the severity of an overdose and selecting the most appropriate therapy are provided. The indications for chelation therapy with deferoxamine, gastric decontamination procedures including use of lavage solutions and whole-bowel irrigation, and adjunctive measures are described. Management of acute iron overdose includes supportive care, GI decontamination, and chelation therapy.