A retrospective case-control study of necrotizing enterocolitis (NEC) affecting infants weighing > 2,000 g at birth was performed to determine those factors which could contribute to the development of NEC. Twenty-four infants met the criteria of definite NEC. For each case the next 2 healthy newborns were matched as controls. When compared with the control group, NEC infants had a significantly higher frequency of prolonged rupture of membranes, chorioamnionitis, Apgar score < 7 at 1 and 5 min, respiratory problems, congenital heart disease, hypoglycemia, and exchange transfusions. Only 3 infants with NEC were healthy newborns with an unremarkable perinatal course before NEC. There were no differences in the frequency of preeclampsia, maternal diabetes, maternal drug abuse, meconium-stained amniotic fluid and polycythemia. These results indicate that most of these more mature infants have a predisposing factor before developing NEC.