Cystic periventricular leukomalacia (PVL) is an ischemic brain lesion that mainly affects preterm infants and causes severe neurological damage. Diagnosis is made by cranial ultrasonography. Objectives of this study were to determine the incidence, to identify associated factors and to evaluate the frequency of neurological abnormality at discharge. Infants with PVL in Switzerland were systematically registered (Swiss Pediatric Surveillance Unit, Swiss Neonatal Network) over three years (1995 to 1997). They were compared to a control group matched for gestational age. Over the three year period 40 infants with PVL defined as at least 2 cysts with diameter = 2 mm in the periventricular region were registered (35 of them were preterm babies). In comparison with the matched controls the infants with PVL had received significantly less frequently antenatal corticosteroids (44 vs 78%, Event Rate Ratio 0.57, 95% Confidence Interval 0.38-0.68), they had lower umbilical cord arterial pH and lower Apgar scores; there was a trend to arterial hypotonia and hypocapnia associated with PVL. The infants of the study group needed more often mechanical ventilation or nasal CPAP (92% versus 67%; ERR 1.38, CI 1.07-1.77) and had more often intracranial hemorrhage (39 versus 14%; ERR 2.8, CI 1.13-6.96). 56% of the infants with PVL were considered abnormal at the neurological examination at discharge compared to 28% in the control group (p < 0.02). The incidence of PVL in Switzerland is 1.2% for preterm infants with a birth weight less than 1500 g. Cranial ultrasonography on infants at risk for PVL is important because 44% of the infants with PVL didn't show neurologic abnormalities at discharge.