There is controversy about the identity of focal intestinal perforation (FIP) and necrotizing enterocolitis (NEC). To elucidate the difference between them, we reviewed their clinical presentations. Over the last 20 years, 39 very-low-birth-weight (VLBW) neonates, including 21 extremely-low-birth-weight neonates, underwent a laparotomy for intestinal perforation without mechanical causes. Nineteen patients had typical findings of NEC, and 8 had FIR FIP is defined as isolated intestinal perforation without gross necrosis. In FIP, the gestational age was significantly lower than in NEC (23.8 +/- 1.8 vs 27.0 +/- 2.5 weeks, P < 0.01). The birth weight (BW) of FIP patients was lower than that of NEC infants (635 134 vs 883 256 g, P < 0.05). The incidence of coexistent respiratory distress syndrome (RDS) was higher in FIP compared to NEC (88% vs 37%, P < 0.05). The age at onset was younger in FIP than NEC (7.3 +/- 2.7 vs 14.4 +/- 7.9 days, P < 0.05). All patients except 1 had the sites of perforation exteriorized. There was a trend toward higher survival in FIP compared to NEC (88% vs 58%, P = 0.136). Our data clearly show differences in BW, gestational age, and association of RDS between FIP and NEC. Based on our data, prematurity and RDS appear to be the major etiologic factors of FIR The present series supports the fact that FIP is a definite clinical entity.