Periventricular leukomalacia is an ischemic lesion in periventricular white matter of premature infants. Hemorrhage into the ischemic area occurs in up to 25% of cases. We report two cases in which the diagnosis of periventricular leukomalacia was made during life with real-time ultrasound scanning. In one case, serial scans demonstrated the evolution of echodense regions, observed in the first 3 days of life, to cystic echolucent areas at 4 weeks. In the second case, periventricular echodense areas did not precede the occurrence of cystic echolucent lesions. This may reflect a more chronic ischemic cerebral insult (consistent with recurrent apnea and bradycardia) rather than a presumed acute episode of cerebral ischemia (with or without secondary hemorrhage) sustained by the first case. Real-time ultrasound scanning is a simple, non-invasive technique with which to document the evolution of periventricular leukomalacia, and thus to define the clinical neurological correlates in the neonatal period.