This prospective study of 130 preterm newborns at less than 34 weeks gestational age has examined the predictive value of abnormalities in continuously recorded newborn blood pressure, heart rate, and oxygen tension during the 4 d following delivery for echosonographically demonstrable cerebral lesions (EDCL) identified in the infant by six months corrected age. EDCL consisting of intraventricular hemorrhage, ventriculomegaly, or hyperechoic parenchymal lesions in the brain were identified in 44 preterm newborns (34%). The incidence of EDCL in preterm newborns with no hypotension or hypoxemia was 13%. The incidence of EDCL was significantly increased in preterm newborns with either hypotension or hypoxemia. The probability of EDCL exceeded 50% when the total exposure to either hypotension or hypoxemia during the 4 d exceeded 50 mmHg-hours, or when newborn hypotension and hypoxemia occurred concurrently. No relationship to hypertension, bradycardia, or tachycardia was detected. These findings indicate that hypotension and hypoxemia in the preterm newborn during the 4 d following delivery are useful risk markers of EDCL.