A 21-day-old infant presented with anemia, conjugated hyperbilirubinemia, hypoproteinemia, and a severe coagulopathy. The hospital course was marked by progressive hepatic failure, encephalopathy, and renal insufficiency. The infant died on day 15 of hospitalization. Postmortem examination showed diffuse hepatic fibrosis and marked siderosis of the liver, pancreas, kidney, adrenal glands, and the duodenal epithelium, with sparing of the reticuloendothelial system. These findings were characteristic of idiopathic neonatal iron-storage disease. Previously reported cases are summarized and discussed. An increased awareness and understanding of this rapidly fatal disorder will be important for genetic counseling and possibly in defining an aberrant mechanism in the handling of iron.