Povidone-iodine is an effective antiseptic, but its topical use has been associated with a number of adverse reactions in burn patients and in neonates as a result of transcutaneous absorption. In particular, high plasma iodine concentrations are known to cause renal failure, metabolic acidosis, and thyroid suppression. Because of the permeable nature of the skin in small infants and the large areas cleaned before cardiac operations, it is possible that significant transcutaneous iodine absorption might occur in this situation. We have studied 17 infants, less than 3 months of age, who were undergoing closed cardiac or thoracic procedures. After povidone-iodine skin preparation in 15 (covering 20% to 30% of body surface area), plasma total iodine concentrations rose fourfold (range, 160% to 1,440%). This increase was significantly different from the preoperative level at 6, 12, 18, and 24 hours. There was no increase in plasma iodine concentration in 2 patients who were not exposed to povidone-iodine or any other iodine-containing compound. We discuss the implications for a topical antisepsis policy in infants.