The multifactorial etiology of cerebral intraventricular hemorrhage (IVH) may involve coagulation disturbances and venous infarction. We tested whether coagulation abnormalities associated with adult venous thrombosis would constitute a risk factor for IVH in newborn infants. In 22 infants (gestational age 24.3--39.9 wk, median 28.0 wk) with neonatal IVH grade II to IV, the frequencies of congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) and a polymorphism in the prothrombin gene (G20210A-FII) were assessed and compared with those observed in 29 premature newborn infants without IVH and in 302 (Gln506-FV) or 526 (G20210A-FII) healthy adults. In infants with IVH, four (18%) heterozygous carriers of Gln506-FV and one (5%) heterozygous carrier of G20210A-FII were found. One infant without IVH was heterozygous for Gln506-FV (3%). When compared with the frequency of Gln506-FV in the general population, the odds ratio for being a carrier of Gln506-FV for patients with IVH was 5.9 (95% confidence interval 1.7--20.3, p = 0.013) and for patients without IVH 0.9 (95% confidence interval 0.1--7.6, p > 0.99). The absolute risk of IVH in a newborn infant with heterozygous Gln506-FV and born before 30 wk of gestation was estimated at 80%, whereas the corresponding risk for all infants born before 30 wk was 14%. Gln506-FV was more common in newborn infants with IVH than in the general population, whereas there was no difference in the frequencies of Gln506-FV in infants without IVH and in the general population. Thus, Gln506-FV may be a risk factor of IVH. The risk of IVH in a premature infant with Gln506-FV or other established thrombophilic coagulation abnormality may be considerable.