We performed a case-control investigation of 43 full-term infants with necrotizing enterocolitis (NEC) to identify possible risk factors and unique features of the disorder in the more mature infant. Two control groups were used. The first consisted of "healthy" term infants. The second was a group of "sick" term infants who did not develop NEC. The 43 term infants with NEC represented 12.7% of all 338 neonates with NEC. The median age at onset of symptoms was 2 days, and 18 infants developed NEC on the first day of life. Two (4.7%) of the 43 affected term infants died, while 35 (11.9%) of 295 preterm infants with the disorder died. Only three of the full-term infants who subsequently developed NEC had entirely unremarkable courses prior to the onset of symptoms. Sick infants, in particular those who are small for gestational age or require exchange transfusions, are at risk for NEC. Several other features that may be associated with the subsequent development of NEC include the following: perinatal asphyxia, presence of umbilical catheters, antecedent respiratory distress, polycythemia, and maternal preeclampsia. Full-term infants with these features should be treated with cautious observation and aggressive management early in the neonatal period should they develop signs and symptoms suggestive of NEC.