Continuous povidone-iodine irrigation is frequently used to treat mediastinitis after median sternotomy and has been considered safe and effective. We describe a 34-month-old patient with mediastinitis after median sternotomy who was treated with continuous povidone-iodine irrigation and who absorbed toxic quantities of iodine (total serum iodine, 9,375 micrograms/dl; normal range, 4.5 to 9.0 micrograms/dl). An unexplained metabolic acidosis developed, along with changes in mental status, and the patient died. This experience and a thorough review of the literature lead us to believe that continuous povidone-iodine irrigation of the mediastinum is contraindicated.