To document the occurrence of classical kernicterus in full-term, otherwise healthy, breast-fed infants. We reviewed the files of 22 cases referred to us by attorneys throughout the United States during a period of 18 years, in which neonatal hyperbilirubinemia was alleged to be responsible for brain damage in apparently healthy, nonimmunized, full-term infants. To qualify for inclusion, these infants had to be born at 37 or more weeks' gestation, manifest the classic signs of acute bilirubin encephalopathy, and have the typical neurologic sequelae. Six infants, born between 1979 and 1991, met the criteria for inclusion. Their peak recorded bilirubin levels occurred 4 to 10 days after birth and ranged from 39.0 to 49.7 mg/dL. All had one or more exchange transfusions. One infant had an elevated reticulocyte count (9%) but no other evidence of hemolysis. The other infants had no evidence of hemolysis, and no cause was found for the hyperbilirubinemia (other than breast-feeding). Although very rare, classic kernicterus can occur in apparently healthy, full-term, breast-fed newborns who do not have hemolytic disease or any other discernible cause for their jaundice. Such extreme elevations of bilirubin are rare, and we do not know how often infants with similar serum bilirubin levels escape harm. We also have no reliable method for identifying these infants early in the neonatal period. Closer follow-up after birth and discharge from the hospital might have prevented some of these outcomes, but rare, sporadic cases of kernicterus might not be preventable unless we adopt an approach to follow-up and surveillance of the newborn that is significantly more rigorous than has been practiced. The feasibility, risks, costs, and benefits of this type of intervention need to be determined.