A case-control study was performed to identify perinatal events associated with intraparenchymal echodensity on cranial ultrasonography--an important antecedent of cerebral palsy in very-low-birthweight infants. Forty-eight infants with birthweight < 1500 g and intraparenchymal echodensity on cranial ultrasound examination and 90 controls with normal cranial ultrasounds were identified within a cohort of 1791 consecutive very-low-birthweight infants born at a regional obstetric referral centre. Data about potential risk factors were obtained from medical records of cases and controls. Among prenatal factors, chorioamnionitis (odds ratio[OR]: 3.2; 95% confidence interval: 1.3, 8.1) and placental abruption (OR 2.6 [1.0, 6.6]) were associated most strongly with an increased risk of intraparenchymal echodensity and pre-eclampsia (OR 0.3 [0.1, 0.8]) was associated most strongly with a decreased risk. When controlling for gestational age, multiple gestation was also associated with an increased risk (OR 2.7 [1.0, 7.5]). Neonatal factors independently associated with an increased risk included low systolic blood pressure (< 33 mmHg in the first 12 h of life; odds ratio 8.0 [2.0, 31.3]), receipt of a fluid bolus in the first 12 h of life (OR 19.7 [4.6, 84.3]), need for cardiopulmonary resuscitation in the first 72 h (OR 6.9 [1.5, 31.3]) and pneumothorax in the first 72 h of life (OR 27.0 [4.3, 167.2]). When analyses were restricted to infants who were not given a fluid bolus, the associations with chorioamnionitis and placental abruption were attenuated. When excluding infants who had a pneumothorax, the associations with placental abruption and multiple gestation were attenuated. Restriction of infants with systolic blood pressure < 33 mmHg resulted in attenuation of associations with pre-eclampsia and multiple gestation. These analyses suggest the possibility that potentially modifiable postnatal events may be involved as intervening factors linking chorioamnionitis, placental abruption and multiple gestation with subsequent intraparenchymal echodensity.