This study tests the hypothesis that histologic placental lesions were significantly related to incidence of early or late germinal matrix/intraventricular hemorrhage (GM/IVH) in infants of less than 32 weeks' gestation independent of maternal or neonatal factors. Maternal and neonatal charts of 406 singleton liveborn nonanomalous infants born at less than 32 weeks' gestation were studied retrospectively for principal indication for delivery, delivery mode, timing of antenatal steroid treatment, diagnosis of labor and augmentation, tocolysis, fetal presentation, and umbilical arterial and venous blood gas values. Extracted from neonatal charts were gestational age, growth measurements, initial hematocrit and white blood cell count, administration of surfactant, and in the first 3 days of life, the use of pressor agents and volume expansion, lowest blood pressure, and data pertinent to respiratory function. Placental histologic examination was reviewed for various lesions, including histologic acute inflammation (graded on a scale of 0 to 4). GM/IVH (grades 1 to 4) diagnosed ultrasonographically less than 72 hours after birth was "early." GM/IVH diagnosed after 72 hours of life was defined as "late." Of the 406 patients, 44 (10.8%) had early GM/IVH; 21 (4.9%) had late GM/IVH. Stepwise logistic regression selected five factors independently related to increased early GM/IVH risk: Histologic acute inflammation (p < 0.002); gestational age in days (p = 0.053); antenatal steroid treatment less than 48 hours before birth (p < 0.035); volume expansion in the neonate (p < 0.30), and magnesium sulfate tocolysis (p < 0.025). Stepwise regression analysis considering the grade of GM/IVH changed the order of variables, with gestational age and use of pressor therapy being more strongly related to higher grade of GM/IVH than amnion inflammation. Delivery mode, presentation, principal indication for delivery, presence/augmentation of labor, mean biophysical profile scores, mean umbilical arterial and venous blood gas values, and surfactant therapy were not related to early GM/IVH in univariate or multivariate analyses. Neonatal factors associated (p < 0.05) with amnion inflammation were volume expansion at delivery and in the first 3 days of life, low mean systolic pressure, low mean oxygen pressure, low initial hematocrit and cord pH, and increased initial WBC and toxic granulations of neutrophils. Only gestational age, and no maternal or placental factors, was significantly related to late GM/IVH. Infants who have placentas with acute amnion inflammation and receive volume expansion, born to mothers who receive less than 48 hour's exposure to antenatal steroids and are selected to receive magnesium sulfate tocolysis, have increased incidence of early but not late GM/IVH. Amnion inflammation is significantly related to early GM/IVH and with early neonatal abnormalities in oxygenation, perfusion, and effective blood volume. Intra-amniotic infection leads to advanced preterm labor, which is unresponsive to tocolysis because of the inflammation. Intra-amniotic inflammation may sensitize the fetus to postpartum stresses or initiate early GM/IVH in utero via cytokine effects on cardiovascular instability.