Intravenous immunoglobulin (IVIG) is a blood derivative that is being evaluated for the prevention and treatment of numerous disorders. Recent studies have suggested beneficial effects from the prophylactic administration of IVIG to very-low-birth-weight neonates. A disadvantage of such therapy is misleading infectious disease serologic assays following administration of IVIG. The authors report a recent case in their neonatal intensive care unit of a 24-week gestational age girl with a misleading positive hepatitis C serology reaction following IVIG administration.