The common side effects associated with the use of prostaglandins in newborn infants include apnoea, hyperthermia, diarrhoea, skin flushing and oedema. Periosteal reaction or cortical thickening of the bones, also known as cortical hyperostosis, is associated with a prolonged use of prostaglandins. This is a radiological diagnosis; therefore, its occurrence is most likely underestimated. We describe an infant who developed cortical hyperostosis simulating osteomyelitis with elevated alkaline phosphatase. The radiologic changes were initially attributed to congenital syphilis. This occurred after a prolonged infusion of prostaglandin E 1 for a cyanotic congenital heart disease.