During the years 1990-4, the prevalence of PL or PERI EFF, unassociated with a clear-cut cause, has risen from 0 to 11% of NBIMC neonatal intensive care unit (NICU) admissions with BW <1000 gms. During the high prevalence years of 1993-4, 150 neonates with BW <1000 gm who survived >7 days were admitted to the NBIMC NICU. Twelve (8%) patients (pts) had either a PL (n=7) or a PERI (n=5) EFF. EFF pts compared to the non-EFF pts (p<0.05), were less likely to survive to discharge (58% vs 90%) and more likely to have: sepsis (58% vs 25%), a PDA (75% vs 40%), more than one central venous line(CVL, 50% vs 16%), any CVL complication (83% vs 25%), and edema complicating a CVL (42% vs 12%), although the EFF occurred when no CVL was in place in 4 of the 12 pts. EFF pts had a lower BW (663 vs 782 gm), longer exposure to oxygen(95 vs 48 days) and ventilator treatment (92 vs 36 days). The EFF fluid was sterile in 11 of 12 pts. It resembled a transudate biochemically but with a mean white cell count of 2675/cu mm with 83% lymphocytes. We conclude that PL or PERI EFF is a serious complication in VLBW neonates. It carries a high mortality risk, is at least indirectly related to CVL use and increases in prevalence with decreasing BW in these VLBW pts.