Prostaglandin E's (PGEs) are used therapeutically in newborn infants to maintain an open ductus arteriosus when there is obstruction to systemic or pulmonary arterial blood flow. These prostaglandins have been shown to have other systemic physiologic effects, such as vasodilation, inhibition of platelet aggregation, and enhancement of chemotactic-factor-mediated polymorphonuclear leukocyte infiltration, with resultant loss of lysosomal granules and possibly the generation of free radicals. We have recently seen previously unreported vascular lesions in 3 infants with hypoplastic left heart syndrome treated with usual therapeutic doses of PGE1 for prolonged periods. At autopsy, pulmonary vascular changes reflecting increased flow were present in each infant. One infant had a necrotizing vasculitis, sometimes associated with infarcts, in the lungs and in small muscular arteries in other organs. The form and severity of the vascular changes appear to be related to the duration of PGE1 administration.