The objective of this study was to examine the role of hypoxic/ischemic factors (antepartum hemorrhage, antenatal betamethasone, emergency cesarean section, APGAR score, ante and postnatal indomethacin, acidosis, hypotension, tension pneumothorax, hypocarbia, oxygen dependency at 3 28 day) and infectious factors (premature rupture of membranes, chorioamnionitis, neonatal sepsis) in the etiology of periventricular leucomalacia (PVL). Patients: 175 infants were born in a pediatric tertiary center at 24-28 weeks' gestation in 1991-1994. They had routine cranial ultrasounds in their first weeks of life and all had a cranial ultrasound at term. A pediatric radiologist, unaware of the infants' neonatal history, revised all the scans and classified them on the basis of the ultrasound at term as normal (control group, n = 126) or PVL(PVL group, n =20). Infants with isolated ventricular dilation (n = 23) or isolated intraventricular hemorrhage (n = 6) at term were excluded. Birthweight (990 ± 199 vs 1040 ± 153 g), gestational age (27.2± 1.3 vs 27.3 ± 1.2 weeks) and percentage of male (52 vs 50%) were similar for the control and PVL groups. Results: Infants with PVL had more tension pneumothorax (15 vs 3%, p <.05), more neonatal sepsis (60 vs 29%, p <.05).and more hypocarbia (70 vs 42%, p <.05) than control infants. Conclusion: Hypocarbia, neonatal sepsis, and tension pneumothorax are significant predictors of PVL.